基因组突变数据分析-ClinVar数据库

探序基因肿瘤研究院

数据库简介：ClinVar是一个免费访问的公共数据库，记录了人类变异和表型之间的关系，并提供了支持性证据（supporting evidence）。ClinVar提供的变异临床意义（clinical significance）判读标准（Assertion Criteria）包含：pathogenic, likely pathogenic, uncertain significance, benign等。

 参考：

人类遗传变异神库 | ClinVar数据库详解

B站-ClinVar数据库介绍

简书-Clinvar数据库

B站-基于ACMG_AMP和ClinGen框架的临床遗传变异分类解读

关于变异的分类问题，https://www.ncbi.nlm.nih.gov/clinvar/docs/clinsig/：

The following table lists the options for germline classification for a submitted record (SCV) in ClinVar and guidance for when each term should be used.

Germline classification	Guidance for use in ClinVar SCV records
Benign	As recommended by ACMG/AMP for variants classified for Mendelian diseases.
Likely benign	As recommended by ACMG/AMP for variants classified for Mendelian diseases.
Uncertain significance	As recommended by ACMG/AMP for variants classified for Mendelian diseases.
Likely pathogenic	As recommended by ACMG/AMP for variants classified for Mendelian diseases.
Pathogenic	As recommended by ACMG/AMP for variants classified for Mendelian diseases.
Likely pathogenic, low penetrance	As recommended by ClinGen for variants with decreased penetrance for Mendelian diseases.
Pathogenic, low penetrance	As recommended by ClinGen for variants with decreased penetrance for Mendelian diseases.
Uncertain risk allele	As recommended by ClinGen for variants with decreased penetrance for Mendelian diseases.
Likely risk allele	As recommended by ClinGen for variants with decreased penetrance for Mendelian diseases.
Established risk allele	As recommended by ClinGen for variants with decreased penetrance for Mendelian diseases.
drug response	A general term for a variant that affects a drug response, not a disease.
association	For variants identified in a GWAS study and further classified for disease.
protective	For variants that decrease the risk of a disorder, including infections.
Affects	For variants that cause a non-disease phenotype, such as lactose intolerance.
conflicting data from submitters	Only for submissions from a consortium, where groups within the consortium have conflicting classifications of a variant but provide a single submission to ClinVar. This value was only used for early submissions from one consortium. Currently, we ask that a consortium come to its own consensus on a variant’s classification before submission to ClinVar.
other	If ClinVar does not have the appropriate term for your submission, we ask that you submit "other" as the classification and include the appropriate term as "Explanation if classification is other or drug response".
not provided	For submissions without a of classification of the variant. The primary goal of ClinVar is to archive variant classifications, so submissions with a classification of "not provided" are limited to: "literature only" submissions that only report a publication about the variant, without providing a classification "research" submissions that provide functional data (e.g. undetectable protein level) but no classification of the variant for a disease "phenotyping only" submissions from clinics or physicians that provide additional information about individuals with the variant, such as observed phenotypes, but do not provide a classification of the variant
'-'	This value may not be submitted. It is used in the file variant_summary.txt.gz in the path  https://ftp.ncbi.nlm.nih.gov/pub/clinvar/tab_delimited/. This file reports  '-' in the ClinicalSignificance column for a variant that was submitted to ClinVar only in combination with another variant (e.g. a submission for classification of a haplotype or a genotype) and was not classified explictly.  In that case, ClinVar has no classification specific to that variant.  To find the record that includes that variant, you can query ClinVar by the AlleleID,e.g. https://www.ncbi.nlm.nih.gov/clinvar/?term=38420[alleleid].