Rare Disease Tiering Interpretation Service Data

Rare Disease Tiering Service

*Mandatory field

Warning

It is highly recommended to read the technical documentation for the rare disease tiering available in this link where, the the algorithm is described and the gene lists used for this analysis are available.

Rare Disease Tiering v1.4.4 produces an Interpreted Genome with the following fields populated

Data DescriptionExample Response

Field Name	Type	Description
comments	array[string]	Always null
variants	array[SmallVariant]	List of small reported variants by rare disease tiering service. An empty list will indicate the absence of reported small variants for this case.
reportUrl	string	Always Null
karyotypes	array[Karyotype]	Always null. Rare Disease Tiering service does not perform analysis for Karyotypes
versionControl*	ReportVersionControl	rare disease tiering data is represented using version 6.0.0 of Interpreted Genome Model. More details: https://gelreportmodels.genomicsengland.co.uk/html_schemas/org.gel.models.report.avro/6.0.0/InterpretedGenome.html#/schema/org.gel.models.report.avro.InterpretedGenome
softwareVersions*	map[string, string]	This map contains the versions of the different software systems used in the analysis, the keys being the software names and the versions are the values.
shortTandemRepeats	array[ShortTandemRepeat]	List of reported STR by tiering. The Short Tandem Repeats array may be empty since not all cases have tiered STRs.
structuralVariants	array[StructuralVariant]	List of structural variants reported by tiering. This version of the tiering will only report on CNVs no other structural variants are expected here.
uniparentalDisomies	array[UniparentalDisomy]	Always null. rare disease tiering service does not perform analysis for uniparentalDisomies
interpretationService*	string	Fixed value. genomics_england_tiering
interpretationRequestId*	string	Full id of the case in the cipapi. Generally something like: SAP-XXXX-XX
chromosomalRearrangements	array[ChromosomalRearrangement]	Always null. Rare Disease Tiering service does not perform analysis for chromosomal Rearrangements
referenceDatabasesVersions*	map[string, string]	This map contains the versions of the different databases used in the analysis, being the database names the keys and the versions the values. For a description of the data sources, please see this table. These are the expected values: "Cancer Analysis Resources": "v1.11" "ClinVar": "2019-06" "1000 genomes project": "ENSEMBL liftover" "DiscovEHR": "GHS Freeze 50 + GeL liftover" "GoNL": "Release 5 + GeL liftover" "COSMIC": "v89" "gnomAD": "2.0.1 + GeL liftover" "ENSEMBL_variation": "90_38" "ENSEMBL_gene": "90_38" "UK10K project": "2016-02-15 + GeL liftover""ENSEMBL_genome": "90_38"
interpretationRequestVersion	integer	Version for the interpretation request. This will be the case version in the cipapi.

interpreted_genome_data: {
comments: null,
variants: [...],
reportUrl: null,
karyotypes: null,
versionControl: {...},
softwareVersions: {},
shortTandemRepeats: null,
structuralVariants: [...],
uniparentalDisomies: null,
interpretationService: "genomics_england_tiering",
interpretationRequestId: "GEL-2534-1",
chromosomalRearrangements: null,
referenceDatabasesVersions: {},
interpretationRequestVersion: 1
},

Rare Disease Tiering v1.4.4 - SmallVariant

Data DescriptionExample Response

Field Name	Type	Description
reportEvents*	array[ReportEvent]	The list of report events for this variant across multiple modes of inheritance, panels and
variantCalls*	array[VariantCall]	List of variant calls across all samples under analysis for this variant
variantAttributes	VariantAttributes	A reported variant
variantCoordinates*	VariantCoordinates	The variant coordinates. Chromosome is either 1-22, X, Y, MT or any other contig in the reference genome, no chr prefix is expected. Position is 1- based. Reference and alternate should never be empty or any character representing emptiness (e.g.: . or -), a VCF-like indel representation is expected.

variants: [
{
    reportEvents: [...],
    variantCalls: [...],
    variantAttributes: {...},
    variantCoordinates: {...}
},
...
]

Rare Disease Tiering v1.4.4 - StructuralVariant

Data DescriptionExample Response

Field Name	Type	Description
leftInsSeq	String	Always null. rare disease tiering does not populate this field
coordinates*	Coordinates	The variant coordinates. Chromosome is either 1-22, X, Y, MT or any other contig in the reference genome, no chr prefix is expected. Position is 1- based. Reference and alternate should never be empty or any character representing emptiness (e.g.: . or -), a VCF-like indel representation is expected. For Structural Variants, reference and alternate fields are not populated.
rightInsSeq	String	Always null. rare disease tiering does not populate this field
variantType	String	Type of structural variant. Expected values for this tiering version are: amplification, deletion
reportEvents*	array[ReportEvent]	The list of report events for this variant across multiple modes of inheritance, panels and
variantCalls*	array[VariantCall]	List of variant calls across all samples under analysis for this variant
variantAttributes	VariantAttributes	A reported variant

structuralVariants: [
{
leftInsSeq: null,
coordinates: {...},
rightInsSeq: null,
variantType: "amplification",
reportEvents: [...],
variantCalls: [...],
variantAttributes: {...}
}
],

Rare Disease Tiering v1.4.4 - ShortTandemRepeats

Data Description

Field Name	Type	Description
coordinates*	Coordinates	The variant coordinates. Chromosome is either 1-22, X, Y, MT or any other contig in the reference genome, no chr prefix is expected. Position is 1- based. Reference and alternate should never be empty or any character representing emptiness (e.g.: . or -), a VCF-like indel representation is expected. For Structural Variants, reference and alternate fields are not populated.
variantCalls*	array[VariantCall]	List of variant calls across all samples under analysis for this variant
reportEvents*	array[ReportEvent]	The list of report events for this variant across multiple modes of inheritance, panels and
variantAttributes	VariantAttributes	A reported variant
shortTandemRepeatReferenceData	ShortTandemRepeatReferenceData	Always null. rare disease tiering does not populate this field

Rare Disease Tiering v1.4.4 - Coordinates

Data DescriptionExample Response

Field Name	Type	Description
end	integer	Position is 1- based
ciEnd	ConfidenceInterval	Always null. rare disease tiering does not populate this field
start	integer	Position is 1- based
ciStart	ConfidenceInterval	Always null. rare disease tiering does not populate this field
assembly	Assembly Enum	Can either be GRCh38 or GRCh37
chromosome	string	Chromosome is either 1-22, X, Y, MT or any other contig in the reference genome, no chr prefix is expected

coordinates: {
end: 5767118,
ciEnd: null,
start: 5367043,
ciStart: null,
assembly: "GRCh37",
chromosome: "3"
}

Rare Disease Tiering v1.4.4 - VariantCoordinates

Data DescriptionExample Response

Field Name	Type	Description
assembly	string	Can either be GRCh38 or GRCh37
chromosome	string	Chromosome is either 1-22, X, Y, MT or any other contig in the reference genome, no chr prefix is expected
position	integer	Position is 1- based
reference	string	Reference should never be empty or any character representing emptiness (e.g.: . or -), a VCF-like indel representation is expected
alternate	string	Alternate should never be empty or any character representing emptiness (e.g.: . or -), a VCF-like indel representation is expected (if there are multiple they will be separated by commas ( , ) )

variantCoordinates: {
assembly: "GRCh37",
chromosome: "14"
position: 21953514,
reference: "C",
alternate: "T",
}

Rare Disease Tiering v1.4.4 - VariantCall

Data DescriptionExample Response

Field Name	Type	Description
sampleId*	string	Sample id
zygosity*	Zygosity(enumeration)	Variant zygosity
alleleOrigins	array[AlleleOrigin]	Fixed value: [germline_variant]. Rare disease tiering analysis is only for germline variants
participantId*	string	Participant id
phaseGenotype	PhaseGenotype	Always null. rare disease tiering does not populate this field
depthAlternate	integer	Integer with the Depth value for the alternate allele.
depthReference	integer	Integer with the Depth value for the reference allele.
numberOfCopies	array[NumberOfCopies]	Alleles for copy number variation. This field is populated for CNV calls.
supportingReadTypes	SupportingReadType(enumeration)	Always null. rare disease tiering does not populate this field
sampleVariantAlleleFrequency	double	Always null. rare disease tiering does not populate this field

variantCalls: [
{
sampleId: "NA19248",
zygosity: "heterozygous",
alleleOrigins: ["germline_variant"],
participantId: "participant_NA19248",
phaseGenotype: null,
depthAlternate: 11,
depthReference: 10,
numberOfCopies: null,
supportingReadTypes: null,
sampleVariantAlleleFrequency: null
}
],

Rare Disease Tiering v1.4.4 - VariantAttributes

Data DescriptionExample Response

Field Name	Type	Description
ihp	integer	Always null. rare disease tiering does not populate this field
fdp50	float	Always null. rare disease tiering does not populate this field
others	map[string]	Always null. rare disease tiering does not populate this field
comments	array[string]	Always null. rare disease tiering does not populate this field
references	map[string]	Always null. rare disease tiering does not populate this field
cdnaChanges	array[string]	List of cdna changes: HGVS nomenclature (e.g.: "ENST00000360004(ENSG00000196126):c.308C]T"). This data is obtain from cellbase (v4.7.1). Cellbase uses ENSMBL 90.
alleleOrigins	array[AlleleOrigin]	Fixed value: [germline_variant]. rare disease tiering analysis is only for germline variants
genomicChanges	array[string]	Always null. rare disease tiering does not populate this field
proteinChanges	array[string]	List of protein changes: HGVS nomenclature (e.g.: "ENSP00000478104:p.Arg2432Cys") from cellbase. NOTE: HGVS protein was introduced in tiering v1.4.4 ("Bill" NGIS release). In interpreted genomes produced by earlier versions, this field will be null.
alleleFrequencies	array[AlleleFrequency]	See table for AlleleFrequency. This field may be an empty array.
variantIdentifiers	VariantIdentifiers	See table for VariantIdentifiers
recurrentlyReported	boolean	Always null. rare disease tiering does not populate this field
additionalNumericVariantAnnotations	map[float]	Always null. rare disease tiering does not populate this field
additionalTextualVariantAnnotations	map[string]	Always null. rare disease tiering does not populate this field

variantAttributes: {
    ihp: null,
    fdp50: null,
    others: null,
    comments: null,
    references: null,
    cdnaChanges: null,
    alleleOrigins: ["germline_variant"],
    genomicChanges: null,
    proteinChanges: null,
    alleleFrequencies: [...],
    variantIdentifiers: {},
    recurrentlyReported: null,
    additionalNumericVariantAnnotations: null,
    additionalTextualVariantAnnotations: {ConsequenceType: "intron_variant"}
},

Rare Disease Tiering v1.4.4 - AlleleFrequency

Data DescriptionExample Response

Field Name	Type	Description
study*	string	The study from where this data comes from. See table.
population*	string	The specific population where this allele frequency belongs. See table.
alternateFrequency*	float	The frequency of the alternate allele

alleleFrequencies: [
    {
    study: "GNOMAD_GENOMES",
    population: "ALL",
    alternateFrequency: 0.21879612
    },
    ...
    ]

Rare Disease Tiering v1.4.4 - VariantIdentifiers

Data DescriptionExample Response

Field Name	Type	Description
dbSnpId	null	string	Variant Identifier in dbSNP format e.g. rs17884070
otherIds	null	array[Identifier]	rare disease tiering always fills in this field with one single element being the id of the variant obtain by concatenating the chromosome the position and the reference allele.
cosmicIds	null	array[string]	Always null. rare disease tiering does not populate this field
clinVarIds	null	array[string]	Always null. rare disease tiering does not populate this field

variantIdentifiers: {
dbSnpId: "rs34647735",
otherIds: null,
cosmicIds: null,
clinVarIds: null
},

Rare Disease Tiering v1.4.4 - ReportEvent

Data DescriptionExample Response

Field Name	Type	Description
tier	Tier [Enum]	rare disease tiering only uses TIER1, TIER2 and TIER3. For a further description on these values please see the technical documentation in this link
score	float	Always null. rare disease tiering does not populate this field
domain	Domain	Always null. Exomiser does not use domain to classify variants.
actions	Actions	Always null. rare disease tiering does not populate this field
genePanel	GenePanel	Always Populated with GenePanel objects associated to this report event.
penetrance	Penetrance (enumeration)	This is the penetrance assumed for scoring or classifying this variant. For a further description on these values please see the technical documentation in this link
phenotypes*	Phenotypes	List of phenotypes relevant to this report event, only populates the nonStandardPhenotype, which always correspond to the clinical indication for which this report event has been issued. For example: {nonStandardPhenotype: disease name present in panelstandardPhenotypes: always null}
roleInCancer	array[RoleInCancer]	Always null. rare disease tiering does not populate this field
reportEventId*	String	Unique identifier for each report event, this is unique across the whole report. Although it is a String, it is always filled with an integer converted to string.
genomicEntities	array[GenomicEntity]	List of all of the genomic entities relevant for this report event. Can be null.
groupOfVariants	integer	This value groups variants that together could explain the phenotype according to the mode of inheritance used. (e.g.: compound heterozygous). All the variants in the same report sharing the same value will be considered in the same group (i.e.: reported together). This value is an integer unique in the whole report. These values are only relevant within the same report.
modeOfInheritance*	ModeOfInheritance (enumeration)	rare disease tiering populates this field with any value from the enumeration. For a further description on these values please see the technical documentation in this link
deNovoQualityScore	float	Can be null or a float when populated.
eventJustification	string	Always null. rare disease tiering does not populate this field
segregationPattern	SegregationPattern (enumeration)	rare disease tiering populates this field with any value from the enumeration. For a further description on these values please see the technical documentation in this link
variantConsequences*	array[VariantConsequence]	Variant consequence ID and name. For each possible consequence type that is compatible with this report event. This information is calculated using cellbase (v4.7.1). Cellbase uses ENSMBL 90 to calculate the impact of the variant in the genes.
vendorSpecificScores	map[string, float]	Always null. rare disease tiering does not populate this field
variantClassification	VariantClassification	Always null. rare disease tiering does not populate this field
fullyExplainsPhenotype	boolean	Always null. rare disease tiering does not populate this field
guidelineBasedVariantClassification	GuidelineBasedVariantClassification	Always null. rare disease tiering does not populate this field
algorithmBasedVariantClassifications	array[AlgorithmBasedVariantClassification]	Always null. rare disease tiering does not populate this field

reportEvents: [
    {
    tier: "TIER3",
    score: null,
    domain: null,
    actions: null,
    genePanel: {...},
    penetrance: "complete",
    phenotypes: {},
    roleInCancer: null,
    reportEventId: "re212097",
    genomicEntities: [...],
    groupOfVariants: 212097,
    modeOfInheritance: "monoallelic",
    deNovoQualityScore: null,
    eventJustification: "test",
    segregationPattern: null,
    variantConsequences: [...],
    vendorSpecificScores: null,
    variantClassification: null,
    fullyExplainsPhenotype: null,
    guidelineBasedVariantClassification: null,
    algorithmBasedVariantClassifications: null
    },
    ...
]

Rare Disease Tiering v1.4.4 - GenePanel

Data DescriptionExample Response

Field Name	Type	Description
panelIdentifier	null	string	Panel ID used
panelName	null	string	Panel name used
panelVersion	null	string	Panel version
source	null	string	source is always panelapp

    genePanel: {
    panelIdentifier: 123
    panelName: "Intellectual disability",
    panelVersion: "1.655",
    source: "panelapp",
    },

Rare Disease Tiering v1.4.4 - GenomicEntities

Data DescriptionExample Response

Field Name	Type	Description
type**	GenomicEntityType Enum	The type of the genomic entity: genomic_region, gene, cytobands and transcript are the expected values for rare disease tiering.
otherIds	array[Identifier]	When type is genomic_region a panelApp region id will be reported: {source: PanelAppidentifier: region name} when the type is cytoband a cytoband id will be reported:{ source: cytoband,identifier: p36.21
ensemblId	string	Ensembl identifier for the feature (e.g, ENST00000544455) This data is obtain from cellbase (v4.7.1). Cellbase uses ENSMBL 90.
geneSymbol	string	HGNC gene symbol e.g. LCE3C. This data is obtain from cellbase (v4.7.1). Cellbase uses ENSMBL 90.

genomicEntities: [
{
type: "transcript",
otherIds: null,
ensemblId: "ENST00000416256",
geneSymbol: "TOX4"
},
{
type: "gene",
otherIds: null,
ensemblId: "ENSG00000092203",
geneSymbol: "TOX4"
}
],

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Last update: 2023-03-01