ClinVar Database

Overview

ClinVar is NCBI's freely accessible archive of reports on relationships between human genetic variants and phenotypes, with supporting evidence. The database aggregates information about genomic variation and its relationship to human health, providing standardized variant classifications used in clinical genetics and research.

When to Use This Skill

This skill should be used when:

• Searching for variants by gene, condition, or clinical significance
• Interpreting clinical significance classifications (pathogenic, benign, VUS)
• Accessing ClinVar data programmatically via E-utilities API
• Downloading and processing bulk data from FTP
• Understanding review status and star ratings
• Resolving conflicting variant interpretations
• Annotating variant call sets with clinical significance

Core Capabilities

1. Search and Query ClinVar

Web Interface Queries

Search ClinVar using the web interface at https://www.ncbi.nlm.nih.gov/clinvar/

Common search patterns:

• By gene: BRCA1[gene]
• By clinical significance: pathogenic[CLNSIG]
• By condition: breast cancer[disorder]
• By variant: NM_000059.3:c.1310_1313del[variant name]
• By chromosome: 13[chr]
• Combined: BRCA1[gene] AND pathogenic[CLNSIG]

Programmatic Access via E-utilities

Access ClinVar programmatically using NCBI's E-utilities API. Refer to references/api_reference.md for comprehensive API documentation including:

• esearch - Search for variants matching criteria
• esummary - Retrieve variant summaries
• efetch - Download full XML records
• elink - Find related records in other NCBI databases

Quick example using curl:

# Search for pathogenic BRCA1 variants
curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=clinvar&term=BRCA1[gene]+AND+pathogenic[CLNSIG]&retmode=json"