Small Variant Details

This page provides more detail about a specific variant. For details on how to use the classification card, and how this is saved in the history, see the recording interpretation page page.

Variant infoGene informationPopulation frequenciesSegregation informationOther databasesPrioritisation results

The variant information card contains basic information about the variant

Key

#	Section	Description
1	Variant coordinates	VCF format of the variant
2	Copy nomenclature button	Copies the variant coordinates in Alamut format
3	External links	Contains a link to IGV (for read depth investigation), and links to external databases and resources for the variant (DECIPHER, GnomAD, UCSC, VarSome and SpliceAI).
4	Header	Contains the same details as sections 1, 2, and 3, as well as the type of SNV,which remain visible upon scrolling.

The gene information card contains a section for each gene that the variant is seen in.

Key

#	Section	Description
1	Gene name	Gene name
2	Gene ID	Ensembl gene ID
3	Links	Linkouts to external resources and databases for the gene (OMIM, PubMed, PanelApp, ClinGen)
4	Transcript table	Table containing details of transcripts for that gene which overlap the variant. A '-' in the table indicates that this data is not available for the transcript. Transcripts are ordered by the following priority: Most severe consequence Mane Select Mane Plus Clinical GENCODE Basic Any transcripts that do not match the above criteria are displayed unordered. The number of associated transcripts to display for each gene can be modified using the drop-down in the table, and pages of the table can be navigated between using the arrow buttons.
5	Transcript (Ensembl ID)	Ensembl ID for the transcript. Clicking on the transcript ID links out to the Ensembl page for the transcript. If the transcript is MANE then a flag will be displayed ('M' for MANE Select and 'M+' for MANE Plus Clinical)
6	CDS change	The c. HGVS nomenclature for the CDS change
7	Protein change	The p. HGVS nomenclature for the protein change
8	Predicted consequences	Predicted consequence types (SO terms) for the transcript. N.B. multiple consequences can be associated with the same transcript. If the consequence is the most severe, an 'S' flag will be displayed
9	Protein ID (Ensembl ID)	Ensembl ID for the protein produced by the transcript

The population frequencies card provides allele frequency details for all available studies for the variant. A table is displayed per study. This could include: GnomAD mitochondrial (only visible for mitochondrial variants), GnomAD genomes, GnomAD exomes, and GEL internal studies.

Key

#	Section	Description
1	Tooltip	Provides additional information about the section
2	Max allele frequency	Maximum allele frequency across all studies. Click on the tooltip for higher granularity (allele count and allele number)
3	Study	Study which contains the subpopulation with the maximum allele frequency across all studies

GnomAD exomes and genomes

Key

#	Section	Description
1	Study name	Name of the study - gnomAD exomes or gnomAD genomes
2	Population	Data is provided by population within the study. Population is only visible where number of alt alleles > 0
3	Alt allele frequency for the variant	Frequency of the variant within the population dataset
4	Number homozygous genotypes	Number of individuals within the population dataset that are homozygous for the variant
5	Number of alt alleles	Number of times the variant is observed within the population dataset
6	Allele number - total number of alleles	Total count of reference alleles and variant alleles observed in the population dataset for that variant

gnomAD mitochondrial

Key

#	Section	Description
1	Population	Data is provided by population within the study. Population is only visible where homoplasmic allele count > 0
2	Homoplasmic allele frequency	Proportion of individuals carrying the homoplasmic variant allele within the population dataset
3	Homoplasmic allele count	Number of individuals within the population dataset carrying the mitochondrial variant in a homoplasmic state
4	Allele number - total number of alleles	Total count of reference alleles and variant alleles observed in the population dataset for that variant. N.B. this value is not available for the GeL dataset

GEL internal

GEL internal population frequency data. Further details can be found in the rare disease pipeline user guide

Key

#	Section	Description
1	Population	Data is provided by population within the study
2	Alt allele frequency for the variant	Frequency of the variant within the population dataset
3	Number of alt alleles	This is not available for the GEL dataset
4	Allele number - total number of alleles	This is not available for the GEL dataset

The segregation information card provides information on variant segregation for the proband and relatives. The table can acommodate up to five individuals. Segregation is calculated per-variant, using the same methods as per the rare disease pipeline segregation page.

N.B. the compound heterozygous segregation filter is currently not supported

Key

#	Section	Description
1	Zygosity	Relationship between the alleles at the locus
2	Proband / Mother / Father etc.	A column per related individual is displayed, up to a maximum of 5
3	Affected status	The affected status of the individual ('Affected', 'Unaffected', or 'Uncertain')
4	Patient ID	GEL patient identifier
5	Sample ID	GEL sample identifier
6	Zygosity	Visual representation of the zygosity for the individual. See below section 'Zygosity visualisation' for further details
7	Alt reads	Number of variant-supporting reads for the individual
8	Ref reads	Number of reference-supporting reads for the individual
9	Total reads	Total number of reads for the individual (ref reads + alt reads)

Zygosity visualisation

Zygosity is visualised according to the below criteria. For mitochondrial variants, Dragen 4 uses AF thresholds to determine tghe plasmy (Heteroplasmic = AF < 0.95, homoplasmic = AF ≥ 0.95).

N.B. As the sample is blood, for mitochondrial variants the plasmy may not be representative of that of the tissue related to the disease

• No call and unknown represent missing data where no genotype is available
• Half missing represents where one allele is observed but the other allele's data is missing

The other databases information card displays a table with information about the variant classifications.

N.B. these annotations are static and added at the time of analysis of the case by the pipeline

ClinVar

Key

#	Section	Description
1	Accession	ClinVar Variation identifier for the variant (uniquely identifies the variant in ClinVar)
2	Review status	ClinVar Level of review supporting the variant classification
3	Submissions	Number of ClinVar submissions contributing to the review status
4	Classification	ClinVar aggregate classification for the variant
5	Interpretation	Totals submissions for each classification category, across all ClinVar submissions for the variant (Pathogenic, Likely Pathogenic, Uncertain significance, Likely benign, Benign)
6	Last submission	Latest submission for the variant at the time of analysis by the pipeline

The prioritisation results card displays the Genomics England Tiering information for the variant for the applied panels. It displays the highest tier assigned to the variant, and the clinical indication for the proband. In the table all prioritisation results for the variant are displayed, showing the relevant gene and associated panel, the tier assigned, the segregation and the mode of inheritance.

N.B. it is important to note that this section is currently not displaying accurate information. This will be rectified in a future release

Key

#	Section	Description
1	Tooltip	Provides additional information about the section
2	Tiering	Button for the Genomics England Rare Disease Tiering tab
3	Highest tier	The highest tier assigned to the variant by Genomics England Rare Disease Tiering
4	Clinical indication	The clinical indication for the proband
5	Tier	Tier applied by the Genomics England Rare Disease Tiering Process
6	Gene	Gene for the Genomics England Rare Disease Tiering result
7	Variant segregation	Variant segregation for the gene
8	Variant MOI	Variant mode of inheritance for the gene
9	Panel name	Name of the panel related to the Genomics England Rare Disease Tiering result, with a link to the GMS signed off PanelApp panel
10	Penetrance	Variant penetrance
11	Learn more about tiering	Link to the Genomics England Rare Disease Genome Analysis Guide