variant-annotationlisted

# Functional Annotation of Genetic Variants with ENCODE Data ## When to Use - User wants to annotate genetic variants with ENCODE regulatory element overlap and functional evidence - User asks about "variant annotation", "regulatory variants", "non-coding variants", or "variant prioritization" - User needs to assess whether a variant falls in an active enhancer, promoter, or TF binding site - User wants to build a multi-evidence variant interpretation combining ENCODE + ClinVar + gnomAD - Example queries: "annotate my GWAS hits with ENCODE regulatory data", "does this variant disrupt a TF binding site?", "prioritize non-coding variants by regulatory impact" Interpret non-coding genetic variation by layering ENCODE functional genomics annotations to identify causal regulatory variants and link them to target genes. ## Scientific Rationale **The question**: "Which of my GWAS/eQTL variants actually disrupt regulatory elements, and what genes do they affect?" Over 90% of disease-associated variants from GWAS fall in non-coding regions of the genome. Without functional annotation, a GWAS locus is just a genomic coordinate — it does not tell you which variant is causal, what regulatory element it disrupts, or which gene it affects. ENCODE provides the richest catalog of functional elements for interpreting these variants. ### The Core Challenge A typical GWAS locus contains dozens to hundreds of variants in linkage disequilibrium (LD) with the lead SNP. The causal variant(s