skills.rest
ClawBio
ClawBioOFFICIAL
Explore all skills by this author →
WebsiteGitHub

rare-high-impact-variants

Count rare loss-of-function variants carried in an annotated VCF using consequence and population frequency.

1.1k|257|Updated Feb 25, 2026
Search Tags:#bioinformatics#genomics#vcf#allele frequency#loss-of-function#rare variants#variant burden
One-click install
npx skills add https://github.com/ClawBio/ClawBio --skill rare-high-impact-variants
Or copy as Structured Prompt for Agent▼
Please help me install this Agent Skill.
Skill: rare-high-impact-variants
Source: https://github.com/ClawBio/ClawBio/tree/main/skills/rare-high-impact-variants
Command: npx skills add https://github.com/ClawBio/ClawBio --skill rare-high-impact-variants

SYSTEM DOCUMENTATION & REQUIREMENTS

What problem does it solve?

Manually identifying rare, high-impact loss-of-function variants in an annotated VCF requires custom scripting and careful handling of consequence terms and population allele frequencies, and mistakes like treating missing frequency data as rarity inflate results. This skill automates that count with a reproducible report.

Core Features & Use Cases

  • Loss-of-function detection: Flags carried variants whose molecular consequence is nonsense, frameshift, splice donor/acceptor, start-lost, or stop-lost.
  • Frequency-based rarity classification: Separates documented-rare variants (AF below threshold, default 0.01) from common ones and from variants with no frequency data, which are never counted as rare.
  • Structured reporting: Produces a markdown report, machine-readable result.json, a CSV table, and a reproducibility bundle with commands and environment files.
  • Use Case: A researcher with a ClinVar-annotated VCF wants to know how many rare loss-of-function variants a sample carries; the skill returns a headline count with per-variant gene, consequence, zygosity, and population AF details.

Quick Start

Run the rare-high-impact-variants skill in demo mode to count rare loss-of-function variants in the bundled synthetic VCF and generate the report.

Frequently Asked Questions about rare-high-impact-variants

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I count rare loss-of-function variants in a VCF file?▼

Run the skill with an annotated VCF via python rare_high_impact_variants.py --input your.vcf --output outdir. It counts carried variants with loss-of-function consequences and documented population allele frequency below the 0.01 threshold, adjustable with --max-af.

What annotations does a VCF need for rare variant analysis?▼

The VCF must carry a molecular consequence field such as ClinVar MC or a VEP/SnpEff consequence, plus a population frequency like AF_TGP, AF_EXAC, AF_ESP, or gnomAD_AF. A raw caller VCF whose AF is the sample genotype frequency will produce meaningless rarity calls.

Does this skill treat variants with missing allele frequency as rare?▼

No. Variants with no population frequency annotation are placed in a separate frequency-unknown bucket and never counted as rare, because absence of a frequency is not evidence of rarity and many such variants are common loss-of-function polymorphisms.

Can this skill find novel genome-wide loss-of-function variants?▼

No. It only counts high-impact variants already catalogued and annotated in the input VCF. Genome-wide novel LoF calling requires a consequence predictor such as VEP, SnpEff, or bcftools csq plus a complete gnomAD frequency reference, which is out of scope for v0.

What dependencies are required to run the variant counting script?▼

Only Python 3.11 or later with the standard library; there are no third-party runtime dependencies. Optional upstream tools like bcftools, VEP, or SnpEff are only needed to produce the annotated input VCF.

Related Skills

Explore More Education & Research Skills→
ClawBioClawBio
1.1k

vcf-annotator

Annotate VCF files with VEP, ClinVar, and gnomAD data.

Official
Intermediate
aks-buildsaks-builds
1

genomics-precision-medicine

Analyze genomic data with variant classification and pharmacogenomics reporting standards.

Community
Advanced
mims-harvardmims-harvard
1.7k

tooluniverse-rare-disease-genomics

Investigate rare disease genetics from disease identification through variant interpretation using Orphanet, GenCC, and ClinVar.

Official
Advanced
google-deepmindgoogle-deepmind
2.8k

credentials

Verifies API keys in .env files and prompts users to add missing credentials safely.

Official
Basic