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Variant annotationsΒΆ

Cases are processed via the bioinformatics pipeline and annotations are added by CellBase. Once a case arrives to the New IB, additional annotations are added from resources that are currently unavailable in CellBase.

Annotation Description Source Static / Live
Transcript and Protein ID annotations (ID, flags, consequences) CellBase Static (limited by CellBase version)
Genes, coding sequence and protein change Coding sequence and protein change CellBase Static (limited by CellBase version)
gnomAD population frequency Population germline allele frequency database CellBase Static (limited by CellBase version)
ClinVar submissions ClinVar Germline Database - accession, review status, submissions, classification, interpretation, latest submission CellBase Static (limited by CellBase version)
Tiering results Tier, segregation, mode of inheritance, penetrance Genomics England Rare Disease Tiering, Genomics England Rare Disease pipeline Static
Exomiser results Exomiser prioritisation results, with associated scores, ranks and allele frequencies Genomics England Rare Disease Tiering, Genomics England Rare Disease pipeline Static
GEL population frequency Internal germline allele frequency database Genomics England dataset Static
Zygosity Variant zygosity VCF genotype, Genomics England Rare Disease pipeline Static (annotated at case ingestion, using the VCF)
Segregation, MOI, penetrance Segregation, MOI and penetrance groupings from the prioritisation results Genomics England Rare Disease Tiering, Genomics England Rare Disease pipeline Static
GMS PanelApp panels Panel name and version, gene and green status GMS PanelApp Static (annotated by the Genomics England Rare Disease Tiering pipeline)
Non-GMS PanelApp panels Panel name and version, gene status, gene mode of inheritance PanelApp Static (annotated at case ingestion. Dataset used for annotation is updated every hour)
CVA CVA entr(y/ies) for the variant, with classification and count CVA Live
OMIM Associated diseases and gene-phenotype mode of inheritance CellBase Static (annotated at case ingestion. Dataset used for annotation is updated every quarter)

The Genome Aggregation Database (gnomAD) is a population frequency database of large-scale sequencing projects from healthy cohorts.

  • CellBase annotates whether a variant is present in gnomAD (exomes, genomes and mitochondrial datasets)
  • The New IB displays the total population germline allele frequency as well as the subpopulations
  • The database version of gnomAD used by CellBase is displayed in the New IB and may not always be the most recent.

Ensembl is a genome browser that provides gene annotations.

  • CellBase annotates each variant with a transcript and protein ID from Ensembl.
  • The New IB displays these annotations in the variant list and variant details page.
  • The database version of Ensembl used by CellBase may not always be the most recent. Please see the latest version of the Rare Disease Genome Analysis guide and CellBase for further details.

ClinVar is a public database of variant and phenotype relationships alongside supporting evidence and clinical interpretation histories.

  • CellBase annotates whether a variant is present in Clinvar.
  • The New IB displays the ClinVar ID, interpretation, review status and number of entries alongside a link to the ClinVar record in the variant list and variant details page for germline variants.
  • The database version of ClinVar used by CellBase is displayed in the New IB and may not always be the most recent. Please see the latest version of the Rare Disease Genome Analysis guide and CellBase for further details.

The GEL PanelApp knowledgebase allows virtual gene panels related to human disorders to be created, stored and queried and is used as the platform for achieving consensus on gene panels in the NHS Genomic Medicine Service (GMS).

  • The Ensembl gene ID of each variant is used to match the variant to Panels in PanelApp
  • The Panels in which the affected gene is present are then shown on the variant list and variant details page

This is a GEL internal population frequency dataset. Further details can be found in the Rare Disease Genome Analysis Guide.

Prioritisation results are the results from the Rare Disease Genomics England Tiering pipeline for the variant and the applied panels. This comprises of various metadata, including Tier, associated gene(s), segregation, mode of inheritance, and penetrance.

For further information, visit the Tiering section in the Genomics England Rare Disease Pipeline user guide.

The Clinical Variant Ark (CVA) is the knowledge base built from NHS Clinical Scientist interpretations of rare disease patients in the 100K Genomes Project and NHS Genomic Medicine Service. For further information, visit the CVA user guide.

Exomiser is a programme that finds potential disease-causing variants from whole-exome or whole-genome sequencing data. All rare disease cases are run through the Exomiser automated variant prioritisation framework.

For further information, visit the Exomiser page in the Genomics England Rare Disease Pipeline user guide.

Abbreviations
Abbreviation Definition
ACGS Association for Clinical Genomic Science
ACMG American College of Medical Genetics and Genomics
CDS Coding DNA Sequence
CNV Copy Number Variant
CVA Clinical Variant Ark
New IB New Interpretation Browser
GEL Genomics England
GMS Genomic Medicine Service
GLH Genomic Laboratory Hub
HGVS Human Genome Variation Society
HTML Hyper Text Markup Language
HSCN Health and Social Care Network (N3)
IGV Integrative Genomics Viewer
IP Interpretation Portal
NGIS National Genomics Informatics System
PID Patient Identifiable Data
QC Quality Control
SO Sequence Ontology
SNV Single Nucleotide Variant
SV Structural Variant
TOMS Test Order Management Service
UAT User Acceptance Testing
VCF Variant Call Format File
WGS Whole Genome Sequencing