ANNOVAR dropped variants... is the MAF filter working?

[jmatés]

Hi all!

I have one question about the variant filtering with the useful ANNOVAR software.

I prepare my input in this way:

$ perl convert2annovar.pl -format vcf4 ~/Desktop/MySample.vcf --allsample -comment -include -outfile ~/Desktop/MySample.avinput

And then I'm filtering with this argument:

$ perl annotate_variation.pl -filter -dbtype 1000g2012apr_all ~/Desktop/MySample.avinput humandb/ -maf_threshold 0.05 -buildver hg19 --comment -reverse -outfile ~/Desktop/MySample_MAF005_1000G

When revising the output I find entries like this... (summarized to avoid disturbing):

1000g2012apr_all 0.04 chr1 21573855 21573855 G A chr1 21573855 rs1076669 G A .................

1000g2012apr_all 0.99 chr1 236882303 236882303 T C chr1 236882303 rs1341864 T C .................

1000g2012apr_all 0.01 chr11 47371578 47371578 G A chr11 47371578 rs3218719 G A .................

...and more...

Why some of the variants have MAFs bigger than 0.05?

Thank you all in advance...

[jmatés]

When I look closer to the problematic variant (rs1341864) both EVS and 1000G have for this variant a MAF under 0.05 (0.007, actually).

May be the program have in consideration the other allele? Does that make sense? And how this may affect to my analysis?

Any insight?

[Knaus]

Take a look at GeneTalk (www.gene-talk.de) where you can filter you variants based on population freq of the 1000 Genomes Project and several other options. Your raw VCF data will be preprocessed and annotated in the background, using data from several databases (dbSNP, HGMD, ESP6500...) and the filtering settings are easy to use and straight forward.
You can sign up for free and and participate in a community driven approach in analyzing NGS data.

[jmatés]

Thank you Knaus for your reply.

However, I'm trying to implement ANNOVAR (not wANNOVAR, but even so I get similar results with this web based version of ANNOVAR) in a variant detection and filtering pipeline.

I found my question interesting to consider and seek an explanation but, another time, so kind by your part for informing me about GeneTalk. I'll take a look!

[jmatés]

I sent my doubt to Dr Wang, the developer, and in a very fast and kind way helped me.

If I want to filter to find possible non-common variants it's better to use the alternative allele frequency command (-aaf) because (-maf) is filtering strictly the minor allele... and sometimes you can find in situations like mine when the minor allele is precisely the reference allele.

Hope this may help someone who may be in my situation. although I know that, on balance, it was a pretty ridiculous question.

For more information see ANNOVAR website in "Accessory programs" section!