ABSTRACT
This chapter shows how to use Jannovar to annotate the variants in a Variant Call Format (VCF) file according to their frequency using the Exome Aggregation Consortium (ExAC) database. It reviews some of the current resources for variant frequency. ExAC data has proven to be extremely useful for estimating the population frequency of variants found in exome studies. Filtering on ExAC reduces the number of candidate protein-altering variants and is most powerful when the highest allele frequency in any one population ('popmax') is used rather than the average ('global') allele frequency. At a 0.1" allele frequency filter, filtering with the ExAC data left an average of 154 variants for analysis, compared to 1090 after filtering against NHLBI GO Exome Sequencing Project (ESP). The variants in typical exomes and genomes display a wide range of allele frequencies. Recent extensions of Jannovar enable it to use the ExAC data to annotate VCF files.
