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Too many (?) variants detected by joint genotyping of 8232 exomes
I am about to finish analyzing 8232 exome samples. I have used GATK 3.8 and 3.6 throughout my workflow, and followed the best practices guideline. After making variant calling by running haplotypecaller in gvcf mode and using standard workflow, I have merged gvcf files hierarchically until all the 8232 samples have been merged. After initial rounds of gvcf merging, I run the program chr by chr and then further dividing the genome into 30-50 Mb pieces in order to reduce computational time. Finally, I started running genotypegvcfs and VQSR on each of the 70 genomic parts. 60 parts have been completed, and a total of 6.4 M variants have been detected. I estimate to get around 7.5M variants when I completely finish the workflow. I suspect that this amount might be too much than expected for that many exomes, but I am not sure; therefore I would like to have your comments. If it is too much indeed, what might be the cause of getting too many false calls? I can write all the commands I have used in this analysis.
At the end, I am planning to select the variants passing filters (I used tranches 99.5 and 99.0 for SNPs and indels, respectively). But I think this will not reduce the amount of variants significantly. I calculated the number of variants with call rate >80 in a few genomic parts, and I found that only around 50% of all variants reach this call rate. My second question is this: is it normal that my vcf files contain so many variants with low calling rate? If I select the variants with PASS flag and call rate >80, can I trust to the remaining set, or do you think getting to many variants with low call rate indicates that the output is unreliable?