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genome-variant-annotation

Annotate variants with functional effects using SnpEff or Ensembl VEP, adding gene impact, population frequencies, and clinical significance.

person作者: TashanworldhubOpenAPI
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Skill: genome-variant-annotation

Use When

  • User wants to annotate variants with gene and transcript impact predictions.
  • User needs to predict functional consequences (missense, nonsense, splice-site, etc.).
  • User wants to add population allele frequencies (gnomAD, 1000 Genomes).
  • User wants to add clinical annotations (ClinVar significance).
  • User needs to compare annotation engines (SnpEff vs VEP).

Inputs

  • Required:
    • Filtered VCF file (.vcf.gz).
  • Optional:
    • Annotator choice: snpeff or vep (default: snpeff).
    • Genome build (default: GRCh38).
    • Cache directory for annotation databases.
    • Additional VEP plugins or fields (e.g., CADD, LOFTEE).
    • Output format (default: VCF).

Workflow

  1. If SnpEff: run snpEff ann with the appropriate database (e.g., GRCh38.105), producing an annotated VCF and summary stats HTML.
  2. If VEP: run vep with --cache, --merged or --refseq, and add plugins (CADD, gnomAD, ClinVar, LOFTEE).
  3. Add fields to each variant: gene symbol, consequence, impact tier (HIGH / MODERATE / LOW / MODIFIER), HGVS notation.
  4. Optionally add population allele frequencies from gnomAD.
  5. Generate summary statistics: variants by impact category, genes with HIGH-impact variants.

Output Contract

  • Annotated VCF file (.vcf.gz).
  • Annotation summary: HTML report (SnpEff) or stats file (VEP).
  • Variant impact distribution (HIGH, MODERATE, LOW, MODIFIER counts).

Limits

  • SnpEff and VEP annotation databases must be pre-downloaded to the cache directory.
  • VEP plugins (CADD, LOFTEE, gnomAD) require separate data file downloads.
  • Annotation databases must match the reference genome build (GRCh37 vs GRCh38).
  • VEP is generally slower but more configurable than SnpEff.
  • Large VCFs (millions of variants) may require significant memory and runtime.
  • Common failure cases:
    • SnpEff database name not matching the reference build (e.g., using hg19 when VCF is on GRCh38).
    • VEP cache directory missing or not matching the installed VEP version.
    • VEP plugin data files (CADD, LOFTEE) not downloaded or path misconfigured.