text: user146: I'm looking for tools to check the quality of a VCF I have of a human genome. I would like to check the VCF against publicly known variants across other human genomes, e.g. how many SNPs are already in public databases, whether insertions/deletions are at known positions, insertion/deletion length distribution, other SNVs/SVs, etc.? I suspect that there are resources from previous projects to check for known SNPs and InDels by human subpopulations.
  What resources exist for this, and how do I do it? 
  
  user280: Your best bet is to use programs that provide you an complete annotation of variants present in your VCF. Two examples are snpEff and Annovar. These programs work on known variants deem different sources and provide you with information on each item in your file, that you can filter after to try to understand the effects of each variant.
  
  user57: The greatest protein coding variant catalogue is definitely ExAC (>65k individuals). They also published a blogpost where they describe how to reproduce figures in the paper (it is a good start how to get familiar with the dataset).
  For the whole-genome variants I would look at the data created by 1000 genomes project (the latest release has more than 3k individuals). The integrated variant call sets can be downloaded though the portal and catalogue of SVs can be found here.
  In this paper (also 1000 genomes project) they speak about non-precise placement of SVs by SV callers. I would keep this in mind for the comparison of your genome to the known variants.
  
  user84: To achieve (at least some of) your goals, I would recommend the Variant Effect Predictor (VEP). It is a flexible tool that provides several types of annotations on an input .vcf file.  I agree that ExAC is the de facto gold standard catalog for human genetic variation in coding regions.  To see the frequency distribution of variants by global subpopulation make sure "ExAC allele frequencies" is checked in addition to the 1000 genomes. 
  Output in the web-browser:
  
  If you download the annotated .vcf, frequencies will be in the INFO field:
  ##INFO=<ID=CSQ,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. Format: Allele|Consequence|IMPACT|SYMBOL|Gene|Feature_type|Feature|BIOTYPE|EXON|INTRON|HGVSc|HGVSp|cDNA_position|CDS_position|Protein_position|Amino_acids|Codons|Existing_variation|DISTANCE|STRAND|FLAGS|SYMBOL_SOURCE|HGNC_ID|TSL|SIFT|PolyPhen|AF|AFR_AF|AMR_AF|EAS_AF|EUR_AF|SAS_AF|AA_AF|EA_AF|ExAC_AF|ExAC_Adj_AF|ExAC_AFR_AF|ExAC_AMR_AF|ExAC_EAS_AF|ExAC_FIN_AF|ExAC_NFE_AF|ExAC_OTH_AF|ExAC_SAS_AF|CLIN_SIG|SOMATIC|PHENO|MOTIF_NAME|MOTIF_POS|HIGH_INF_POS|MOTIF_SCORE_CHANGE
  
  The previously mentioned Annovar can also annotate with ExAC allele frequencies.  Finally, should mention the newest whole-genome resource, gnomAD.
  
original_text: 146: <p>I'm looking for tools to check the quality of a VCF I have of a human genome. I would like to check the VCF against publicly known variants across other human genomes, e.g. how many SNPs are already in public databases, whether insertions/deletions are at known positions, insertion/deletion length distribution, other SNVs/SVs, etc.? I suspect that there are resources from previous projects to check for known SNPs and InDels by human subpopulations.</p>
  
  <p>What resources exist for this, and how do I do it? </p>
   280: <p>Your best bet is to use programs that provide you an complete annotation of variants present in your VCF. Two examples are <a href="http://snpeff.sourceforge.net" rel="nofollow noreferrer">snpEff</a> and <a href="http://annovar.openbioinformatics.org/en/latest/" rel="nofollow noreferrer">Annovar</a>. These programs work on known variants deem different sources and provide you with information on each item in your file, that you can filter after to try to understand the effects of each variant.</p>
   57: <p>The greatest <strong>protein</strong> coding variant catalogue is definitely <a href="http://www.nature.com/nature/journal/v536/n7616/full/nature19057.html" rel="nofollow noreferrer">ExAC</a> (>65k individuals). They also published a <a href="https://macarthurlab.org/2016/03/17/reproduce-all-the-figures-a-users-guide-to-exac-part-2/" rel="nofollow noreferrer">blogpost</a> where they describe how to reproduce figures in the paper (it is a good start how to get familiar with the dataset).</p>
  
  <p>For the <strong>whole-genome</strong> variants I would look at the data created by <a href="http://www.internationalgenome.org/" rel="nofollow noreferrer">1000 genomes</a> project (the latest release has more than 3k individuals). The integrated variant call sets can be downloaded though the <a href="http://www.internationalgenome.org/data-portal/data-collection/phase-3" rel="nofollow noreferrer">portal</a> and catalogue of SVs can be found <a href="http://www.internationalgenome.org/phase-3-structural-variant-dataset" rel="nofollow noreferrer">here</a>.</p>
  
  <p>In <a href="http://www.nature.com/nature/journal/v526/n7571/full/nature15394.html" rel="nofollow noreferrer">this</a> paper (also 1000 genomes project) they speak about non-precise placement of SVs by SV callers. I would keep this in mind for the comparison of your genome to the known variants.</p>
   84: <p>To achieve (at least some of) your goals, I would recommend the <a href="http://grch37.ensembl.org/Homo_sapiens/Tools/VEP" rel="noreferrer">Variant Effect Predictor (VEP)</a>. It is a flexible tool that provides several types of annotations on an input .vcf file.  I agree that ExAC is the <em>de facto</em> gold standard catalog for human genetic variation in coding regions.  To see the frequency distribution of variants by global subpopulation make sure "ExAC allele frequencies" is checked in addition to the 1000 genomes. <a href="https://i.stack.imgur.com/zDUTT.jpg" rel="noreferrer"><img src="https://i.stack.imgur.com/zDUTT.jpg" alt="VEP ExAC"></a></p>
  
  <p>Output in the web-browser:
  <a href="https://i.stack.imgur.com/0OCCY.jpg" rel="noreferrer"><img src="https://i.stack.imgur.com/0OCCY.jpg" alt="VEP_ExAC_res"></a></p>
  
  <p>If you download the annotated .vcf, frequencies will be in the <code>INFO</code> field:</p>
  
  <pre><code>##INFO=&lt;ID=CSQ,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. Format: Allele|Consequence|IMPACT|SYMBOL|Gene|Feature_type|Feature|BIOTYPE|EXON|INTRON|HGVSc|HGVSp|cDNA_position|CDS_position|Protein_position|Amino_acids|Codons|Existing_variation|DISTANCE|STRAND|FLAGS|SYMBOL_SOURCE|HGNC_ID|TSL|SIFT|PolyPhen|AF|AFR_AF|AMR_AF|EAS_AF|EUR_AF|SAS_AF|AA_AF|EA_AF|ExAC_AF|ExAC_Adj_AF|ExAC_AFR_AF|ExAC_AMR_AF|ExAC_EAS_AF|ExAC_FIN_AF|ExAC_NFE_AF|ExAC_OTH_AF|ExAC_SAS_AF|CLIN_SIG|SOMATIC|PHENO|MOTIF_NAME|MOTIF_POS|HIGH_INF_POS|MOTIF_SCORE_CHANGE
  </code></pre>
  
  <p>The previously mentioned Annovar can also <a href="http://doc-openbio.readthedocs.io/projects/annovar/en/latest/user-guide/filter/#exac-annotations" rel="noreferrer">annotate with ExAC allele frequencies</a>.  Finally, should mention the newest whole-genome resource, <a href="http://gnomad.broadinstitute.org/" rel="noreferrer">gnomAD</a>.</p>
  