ClinVar — NCBI Clinical Variant Database

Overview

ClinVar is a public repository of clinical interpretations of genomic variants, operated by NCBI/NIH since 2013. It aggregates variant-phenotype relationships submitted by clinical laboratories, research groups, and expert panels worldwide, and assigns each variant a clinical significance classification based on submitted evidence. Variants are identified using HGVS notation and are increasingly assigned VRS globally unique computed identifiers for cross-system deduplication. ClinGen expert panels submit curated variant classifications that receive the highest evidence tier and take precedence over individual laboratory submissions.

Content and Classification

• Clinical significance is classified on a five-tier scale: Pathogenic, Likely pathogenic, Uncertain significance (VUS), Likely benign, and Benign.
• Evidence quality is rated on a one-to-four star scale reflecting the number and concordance of submissions, with ClinGen expert panel reviews at the top tier.
• Variant types include single nucleotide variants, indels, copy number variants, and structural variants.
• Disease associations are coded using OMIM MIM numbers, MedGen identifiers, MONDO, and HPO terms.

Connections

• relatedTo: ClinGen (ClinGen expert panels provide the highest-tier curated variant classifications)
• relatedTo: dbSNP (cross-referenced for variant identifiers)
• relatedTo: OMIM (disease associations coded using OMIM MIM numbers)
• relatedTo: HPO (phenotype terms used for variant-disease associations)
• relatedTo: MONDO (disease ontology used for variant-disease associations)
• implements: VCF
• implements: VRS

Resources

• https://www.ncbi.nlm.nih.gov/clinvar/
• https://www.ncbi.nlm.nih.gov/books/NBK174587/ (NCBI Handbook, ClinVar)
• https://clinicalgenome.org (ClinGen, expert variant curation)
• https://gnomad.broadinstitute.org (gnomAD, population allele frequencies)
• https://vrs.ga4gh.org (VRS, globally unique variant identifiers)