bio-variant-calling-clinical-interpretation

ClinVar Annotation

Goal: Annotate variants with ClinVar clinical significance and filter by pathogenicity.

Approach: Download the ClinVar VCF, add CLNSIG/CLNDN/CLNREVSTAT fields with bcftools annotate, then filter by significance level.

"Find pathogenic variants in my VCF" → Cross-reference variants against ClinVar clinical assertions and extract those classified as pathogenic or likely pathogenic.

Exclude benign

bcftools view -e 'INFO/CLNSIG~"Benign" || INFO/CLNSIG~"Likely_benign"'
with_clinvar.vcf.gz -Oz -o not_benign.vcf.gz

## ClinVar Significance Levels

| CLNSIG | Meaning | Action |
|--------|---------|--------|
| Pathogenic | Disease-causing | Report |
| Likely_pathogenic | Probably disease-causing | Report with caveat |
| Uncertain_significance | VUS | May report, needs follow-up |
| Likely_benign | Probably not disease-causing | Usually exclude |
| Benign | Not disease-causing | Exclude |
| Conflicting | Multiple interpretations | Manual review |