Atlas / Skills / freedomintelligence / Variant Annotation

Variant AnnotationSAFE

skills/freedomintelligence/variant-annotation

The largest open-source medical AI skills library for OpenClaw🦞.

Verdict
SAFE
Grade
B
Trust score
89 /100
Version
—
Hosts
—
License
—
Stars
3,053
01

Overview

The largest open-source medical AI skills library for OpenClaw🦞.

Read from source at commit 29f31a89230cOBSERVED · 2026-10-08
02

What it tells the agent

The instruction file, verbatim from the audited commit — this is the text the model reads, and the surface the audit's instruction layer examines. Quoted here so you can judge it without cloning anything.

<!--
# COPYRIGHT NOTICE
# This file is part of the "Universal Biomedical Skills" project.
# Copyright (c) 2026 MD BABU MIA, PhD <[email protected]>
# All Rights Reserved.
#
# This code is proprietary and confidential.
# Unauthorized copying of this file, via any medium is strictly prohibited.
#
# Provenance: Authenticated by MD BABU MIA

-->

---
name: bio-variant-annotation
description: Comprehensive variant annotation using bcftools annotate/csq, VEP, SnpEff, and ANNOVAR. Add database annotations, predict functional consequences, and assess clinical significance. Use when annotating variants with functional and clinical information.
tool_type: mixed
primary_tool: VEP
measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes.
allowed-tools:
  - read_file
  - run_shell_command
---

# Variant Annotation

## Tool Comparison

| Tool | Best For | Speed | Output |
|------|----------|-------|--------|
| bcftools csq | Simple consequence prediction | Fast | VCF |
| VEP | Comprehensive with plugins | Moderate | VCF/TXT |
| SnpEff | Fast batch annotation | Fast | VCF |
| ANNOVAR | Flexible databases | Moderate | TXT |

## bcftools annotate

### Add Annotations from Database

```bash
bcftools annotate -a dbsnp.vcf.gz -c ID input.vcf.gz -Oz -o annotated.vcf.gz
```

### Annotation Columns (`-c`)

| Option | Description |
|--------|-------------|
| `ID` | Copy ID column |
| `INFO` | Copy all INFO fields |
| `INFO/TAG` | Copy specific INFO field |
| `+INFO/TAG` | Add to existing values |

### Add rsIDs from dbSNP

```bash
bcftools annotate -a dbsnp.vcf.gz -c ID input.vcf.gz -Oz -o with_rsids.vcf.gz
```

### Add Multiple Annotations

```bash
bcftools annotate -a database.vcf.gz -c ID,INFO/AF,INFO/CAF input.vcf.gz -Oz -o annotated.vcf.gz
```

### Add from BED/TAB Files

```bash
# BED with 4th column as annotation
bcftools annotate -a regions.bed.gz -c CHROM,FROM,TO,INFO/REGION \
    -h <(echo '##INFO=<ID=REGION,Number=1,Type=String,Description="Region name">') \
    input.vcf.gz -Oz -o annotated.vcf.gz

# Tab file: CHROM POS VALUE
bcftools annotate -a annotations.tab.gz -c CHROM,POS,INFO/SCORE \
    -h <(echo '##INFO=<ID=SCORE,Number=1,Type=Float,Description="Custom score">') \
    input.vcf.gz -Oz -o annotated.vcf.gz
```

### Remove Annotations

```bash
bcftools annotate -x INFO/DP,INFO/MQ input.vcf.gz -Oz -o clean.vcf.gz
bcftools annotate -x INFO input.vcf.gz -Oz -o minimal.vcf.gz  # Remove all INFO
```

### Set ID from Fields

```bash
bcftools annotate --set-id '%CHROM\_%POS\_%REF\_%ALT' input.vcf.gz -Oz -o with_ids.vcf.gz
```

## bcftools csq

Simple consequence prediction using GFF annotation.

```bash
bcftools csq -f reference.fa -g genes.gff3.gz input.vcf.gz -Oz -o consequences.vcf.gz
```

### Consequence Types

| Consequence | Description |
|-------------|-------------|
| `synonymous` | No amino acid change |
| `missense` | Amino acid change |
| `stop_gained` | Introduces stop codon |
| `frameshift` | Changes reading frame |
| `splice_donor/acceptor` | Affects splicing |

## Ensembl VEP

### Installation

```bash
conda install -c bioconda ensembl-vep
vep_install -a cf -s homo_sapiens -y GRCh38 --CONVERT
```

### Basic Annotation

```bash
vep -i input.vcf -o output.vcf --vcf --cache --offline
```

### Comprehensive Annotation

```bash
vep -i input.vcf -o output.vcf \
    --vcf \
    --cache --offline \
    --species homo_sapiens \
    --assembly GRCh38 \
    --everything \
    --fork 4
```

### --everything Enables

- `--sift b` - SIFT predictions
- `--polyphen b` - PolyPhen predictions
- `--hgvs` - HGVS nomenclature
- `--symbol` - Gene symbols
- `--canonical` - Canonical transcript
- `--af` - 1000 Genomes frequencies
- `--af_gnomade/g` - gnomAD frequencies
- `--pubmed` - PubMed IDs

### Filter by Impact

```bash
vep -i input.vcf -o output.vcf --vcf \
    --cache --offline \
    --pick \
    --filter "IMPACT in HIGH,MODERATE"
```

### Plugins

```bash
# CADD scores
vep -i input.vcf -o output.vcf --vcf \
    --cache --offline \
    --plugin CADD,whole_genome_SNVs.tsv.gz

# dbNSFP (multiple predictors)
vep -i input.vcf -o output.vcf --vcf \
    --cache --offline \
    --plugin dbNSFP,dbNSFP4.3a.gz,ALL

# Multiple plugins
vep -i input.vcf -o output.vcf --vcf \
    --cache --offline \
    --plugin CADD,cadd.tsv.gz \
    --plugin dbNSFP,dbnsfp.gz,SIFT_score,Polyphen2_HDIV_score \
    --plugin SpliceAI,spliceai.vcf.gz
```

### VEP Output Fields

| Field | Description |
|-------|-------------|
| Consequence | SO term (e.g., missense_variant) |
| IMPACT | HIGH, MODERATE, LOW, MODIFIER |
| SYMBOL | Gene symbol |
| HGVSc/HGVSp | HGVS coding/protein change |
| SIFT/PolyPhen | Pathogenicity predictions |

## SnpEff

### Installation

```bash
conda install -c bioconda snpeff
snpEff download GRCh38.105
```

### Basic Annotation

```bash
snpEff ann GRCh38.105 input.vcf > output.vcf
```

### With Statistics

```bash
snpEff ann -v -stats stats.html -csvStats stats.csv GRCh38.105 input.vcf > output.vcf
```

### Filter by Impact

```bash
snpEff ann GRCh38.105 input.vcf | \
    SnpSift filter "(ANN[*].IMPACT = 'HIGH')" > high_impact.vcf
```

### SnpEff Impact Categories

| Impact | Examples |
|--------|----------|
| HIGH | Stop gained, frameshift, splice donor/acceptor |
| MODERATE | Missense, inframe indel |
| LOW | Synonymous, splice region |
| MODIFIER | Intron, intergenic, UTR |

### SnpSift Database Annotations

```bash
# dbSNP
SnpSift annotate dbsnp.vcf.gz input.vcf > annotated.vcf

# ClinVar
SnpSift annotate clinvar.vcf.gz input.vcf > annotated.vcf

# dbNSFP
SnpSift dbnsfp -db dbNSFP4.3a.txt.gz input.vcf > annotated.vcf

# Chain multiple
snpEff ann GRCh38.105 input.vcf | \
    SnpSift annotate dbsnp.vcf.gz | \
    SnpSift annotate clinvar.vcf.gz > fully_annotated.vcf
```

### SnpSift Filtering

```bash
SnpSift filter "(QUAL >= 30) & (DP >= 10)" input.vcf > filtered.vcf
SnpSift filter "(exists CLNSIG) & (CLNSIG has 'Pathogenic')" input.vcf > pathogenic.vcf
```

## ANNOVAR

03

Trust audit

SAFEgrade B · trust 89/100 Nothing in the source contradicts what it says it does. Grade A is reserved for packages that have also passed the behavioural sandbox.

LayerWhat it checksResult
L0Provenance & inventoryPASS
L1Static analysis of the codePASS
L2Instruction surface (what it tells the agent)PASS
L3Class-specific surfacePASS
L4Behavioural (sandbox)SKIPPED

What the source does

Filesystem
none-observed
Network
none-observed
Shell
none-observed
Dependencies
pinned
Secrets in source
none-found

Findings (1)

LOWInventory / provenance · skill.no_frontmatter · CWE-1104
SKILL.md:1
Why it matters. SKILL.md lacks name/description frontmatter

Gates applied: no_behavioural_pass.

Audited 2026-10-08 · audit v0.4.1 · source sha 29f31a89230cfull audit observations/trust-audit/skill/freedomintelligence__variant-annotation.json · Report an issue / request a re-scan
04

Audit history

Every audit this skill has had.

DateSourceVerdictGradeScoreChange
2026-10-0829f31a89230cSAFEB89first audit
05

Questions

What does the Variant Annotation skill do?

The largest open-source medical AI skills library for OpenClaw🦞.

Is Variant Annotation safe to install?

The audit found nothing in the source that contradicts what it says it does, and graded it B (89/100). Grade A is held back for packages that have also passed a sandboxed behavioural run, which is why a clean skill reads B.

What can Variant Annotation access on my machine?

The audit observed no filesystem, network or shell use at all in its source.

How current is this page?

The grade is for one exact copy of the source (29f31a89230c), read on 2026-10-08. The repository is watched, and a new audit runs when it changes — this is the first audit.

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