在很久以前的我直播基因组活动，我提到过这个数据库： 【直播】我的基因组67：clinvar数据库
不过，那个时候遗传背景知识不够，其实并没有很好的理解它，现在有机会重新学习一下，可以使用以下代码下载并且注释到clinvar数据库
wget https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/clinvar_20180429.vcf.gz
wget https://ftp.ncbi.nlm.nih.gov/pub/clinvar/vcf_GRCh38/clinvar_20180429.vcf.gz.tbi
java -jar ~/biosoft/SnpEff/snpEff/SnpSift.jar annotate clinvar_20180429.vcf.gz merge_snpeff.vcf >merge_clinvar.vcf
得到的注释信息的描述是：
##SnpSiftCmd="SnpSift annotate clinvar_20180429.vcf.gz merge_snpeff.vcf" ##INFO=<ID=CLNDISDBINCL,Number=.,Type=String,Description="For included Variant: Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN"> ##INFO=<ID=DBVARID,Number=.,Type=String,Description="nsv accessions from dbVar for the variant"> ##INFO=<ID=CLNSIGCONF,Number=.,Type=String,Description="Conflicting clinical significance for this single variant"> ##INFO=<ID=AF_TGP,Number=1,Type=Float,Description="allele frequencies from TGP"> ##INFO=<ID=MC,Number=.,Type=String,Description="comma separated list of molecular consequence in the form of Sequence Ontology ID|molecular_consequence"> ##INFO=<ID=AF_EXAC,Number=1,Type=Float,Description="allele frequencies from ExAC"> ##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB"> ##INFO=<ID=ORIGIN,Number=.,Type=String,Description="Allele origin. One or more of the following values may be added: 0 - unknown; 1 - germline; 2 - somatic; 4 - inherited; 8 - paternal; 16 - maternal; 32 - de-novo; 64 - biparental; 128 - uniparental; 256 - not-tested; 512 - tested-inconclusive; 1073741824 - other"> ##INFO=<ID=CLNVI,Number=.,Type=String,Description="the variant's clinical sources reported as tag-value pairs of database and variant identifier"> ##INFO=<ID=CLNVC,Number=1,Type=String,Description="Variant type"> ##INFO=<ID=AF_ESP,Number=1,Type=Float,Description="allele frequencies from GO-ESP"> ##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression."> ##INFO=<ID=CLNDNINCL,Number=.,Type=String,Description="For included Variant : ClinVar's preferred disease name for the concept specified by disease identifier s in CLNDISDB"> ##INFO=<ID=CLNVCSO,Number=1,Type=String,Description="Sequence Ontology id for variant type"> ##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant"> ##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN"> ##INFO=<ID=CLNREVSTAT,Number=.,Type=String,Description="ClinVar review status for the Variation ID"> ##INFO=<ID=CLNSIGINCL,Number=.,Type=String,Description="Clinical significance for a haplotype or genotype that includes this variant. Reported as pairs of VariationID:clinical significance."> ##INFO=<ID=ALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
记录最多的基因是
zcat clinvar_20180429.vcf.gz|perl -alne '{/GENEINFO=(.*?):/;print $1 if $1}'|sort |uniq -c |sort -k 1,1nr >gene.clinvar.freq
head gene.clinvar.freq
9800 TTN
9038 BRCA2
6311 BRCA1
4987 ATM
4498 APC
3312 TSC2
3114 MSH6
2888 NF1
2653 MSH2
2223 LDLR
记录的致病情况最多的基因是
zcat clinvar_20180429.vcf.gz|perl -alne '{/GENEINFO=(.*?):/;$g=$1;/CLNSIG=(.*?);/;print "$g\t$1" if $1}'| sort |uniq -c |sort -k 1,1nr >gene_sign.clinvar.freq
head gene_sign.clinvar.freq
5218 TTN Uncertain_significance
3293 BRCA2 Uncertain_significance
2665 BRCA2 Pathogenic
2523 ATM Uncertain_significance
2162 BRCA1 Pathogenic
1897 APC Uncertain_significance
1887 TTN Likely_benign
1817 BRCA1 Uncertain_significance
1651 MSH6 Uncertain_significance
1465 BRCA2 Likely_benign
grep Pathogenic gene_sign.clinvar.freq|head
2665 BRCA2 Pathogenic
2162 BRCA1 Pathogenic
691 LDLR Pathogenic
594 MSH2 Pathogenic
571 MLH1 Pathogenic
544 COL4A5 Pathogenic
536 NF1 Pathogenic
469 DMD Pathogenic
467 MSH6 Pathogenic
466 APC Pathogenic
看看是否有被专家审核
zcat clinvar_20180429.vcf.gz|perl -alne '{/GENEINFO=(.*?):/;$g=$1;/CLNSIG=(.*?);/;$t=$1;/CLNREVSTAT=(.*?);/;print "$g\t$t\t$1" if $1}'| sort |uniq -c |sort -k 1,1nr >gene_sign_review.clinvar.freq
[jianmingzeng@jade anno]$ head gene_sign_review.clinvar.freq
4200 TTN Uncertain_significance criteria_provided,_single_submitter
2065 BRCA2 Pathogenic reviewed_by_expert_panel
1915 BRCA2 Uncertain_significance criteria_provided,_single_submitter
1666 BRCA1 Pathogenic reviewed_by_expert_panel
1639 TTN Likely_benign criteria_provided,_single_submitter
1597 ATM Uncertain_significance criteria_provided,_single_submitter
1251 APC Uncertain_significance criteria_provided,_single_submitter
1200 TTN Conflicting_interpretations_of_pathogenicity criteria_provided,_conflicting_interpretations
1174 TSC2 not_provided no_assertion_provided
grep BRCA2 gene_sign_review.clinvar.freq|grep Pathogenic 2065 BRCA2 Pathogenic reviewed_by_expert_panel 436 BRCA2 Pathogenic criteria_provided,_single_submitter 94 BRCA2 Pathogenic criteria_provided,_multiple_submitters,_no_conflicts 70 BRCA2 Pathogenic no_assertion_criteria_provided