ClinVarome annotation

Overview

ClinVarome is a list of genes involved in human disease, based on ClinVar database extraction via Genome Alert!. ClinVarome annotation allows enhanced ClinVarome with useful annotations for genetic diagnostics.

It provides for each gene:

Clinical features extracted from clinVCF VCF file
Molecular consequences reported
Date of first and last apparition of pathogenic variant
Number of reported (likely) pathogenic variants

Based on the following features, the annotation provides also a clinical validity score for genes generated by a Agglomerative Clustering model :

Date between first and last apparition of pathogenic variant
Number of reported (likely) pathogenic variants
Highest review confidence variant status in (likely) pathogenic variant
Highest ACMG classification variant status

ClinVarome annotation is developped in python > 3.6, and need Genome Alert! processed data.

ClinVarome tool is a part of the Genome Alert! framework - Website https://genomealert.univ-grenoble-alpes.fr/.

Quick start

ClinVarome annotation need for a ClinVar release :

a VCF file from ClinVCF
a ClinVarome file from Variant Alert!
a concatenated file of all Variant Alert! compare-variant output (compare-variant_total.tsv.gz)
a concatenated file of all Variant Alert! compare-gene output (compare-gene_total.tsv.gz)

Run ClinVarome

poetry install
#For testing
mkdir OUTPUT_DIR
poetry run clinvarome/clinvarome_annotation.py \
  --vcf tests/full_data/clinvar_GRCh38_{latest}.vcf.gz \
  --clinvarome tests/full_data/clinvarome_{latest}.tsv \
  --compare-gene tests/full_data/compare-gene_total.tsv.gz \
  --compare-variant tests/full_data/compare-variant_total.tsv.gz \
  --output-dir OUTPUT_DIR/

Usage

usage: clinvarome_annotation.py [-h] --vcf VCF_FILE --clinvarome CLINVAROME
                                --compare-gene COMPARE_GENE --compare-variant
                                COMPARE_VARIANT [--max-date MAX_DATE]
                                [--gnomad] [--manual-score] --output-dir
                                OUTPUT_DIR

Add additional annotations to the ClinVarome.

optional arguments:
  -h, --help              show this help message and exit
  --vcf        VCF_FILE   vcf input from clinVCF
  --clinvarome CLINVAROME
                          ClinVarome file from Variant Alert! to be annotated.
  --compare-gene COMPARE_GENE
                          Variant Alert! compare gene concatenation file of all
                          previous ClinVar release.
  --compare-variant COMPARE_VARIANT
                          Variant Alert! compare variant concatenation file of
                          all previous ClinVar release.
  --gnomad                Add max pathogenic gnomAD filtered allele frequency
                          for each gene, if clinVCF is annotated with gnomAD v3
                          by vcfanno.
  --output-dir OUTPUT_DIR
                          Path to the output folder.

Output format

ClinVarome annotation generate an enhanced ClinVarome TSV (file with additional suffix _clinvarome_annotation.tsv).

How to cite

If you use a tool of the Genome Alert! framework, please cite:

Yauy et al., Genome Alert!: a standardized procedure for genomic variant reinterpretation and automated genotype-phenotype reassessment in clinical routine. medRxiv (2021). https://doi.org/10.1101/2021.07.13.21260422

License

ClinVarome is licensed under the Apache License, Version 2.0. See LICENSE for the full license text.

Misc

ClinVarome is a part of the Genome Alert! framework, a collaboration of :

SeqOne / clinvarome