Clarification on Frequency Filtering in GENOMISER (WGS Data) #606
Description
I'm currently working with whole genome sequencing (WGS) data and encountering some issues with variant filtering in Exomiser. I'm attaching my .yml configuration file for your reference, as well as a list of example variants that have passed the filters. [Working with both small and structural variants]
Despite setting the frequencyFilter to { maxFrequency: 1.0 }, I am still seeing variants with relatively high population frequencies in the output. For example, some observed frequencies include:
#RANK ID GENE_SYMBOL EXOMISER_GENE_COMBINED_SCORE EXOMISER_GENE_PHENO_SCORE EXOMISER_GENE_VARIANT_SCORE EXOMISER_VARIANT_SCORE CONTRIBUTING_VARIANT MAX_FREQ_SOURCE MAX_FREQ ALL_FREQ MAX_PATH_SOURCE MAX_PATH ALL_PATH
1 14-90410059-ATTTTTTT-A_AD CALM1 0.9885 1 0.8005 0.8005 1 CADD 0.80047375 CADD=0.80047375,REMM=0.578913
1 14-90378703-CA-C_AD CALM1 0.9885 1 0.8005 0.5487 0 REMM 0.548673 CADD=0.20567179,REMM=0.548673
2 19-1102515-C-CAAAAAAAAAA_AR GPX4 0.9696 0.8681 0.8415 0.8952 1 GNOMAD_G_SAS 0.038580246 GNOMAD_G_AFR=0.026418682,GNOMAD_G_AMR=0.02647604,GNOMAD_G_NFE=0.017146775,GNOMAD_G_SAS=0.038580246 CADD 0.9 CADD=0.9,REMM=0.776185
2 19-1098935-G-A_AR GPX4 0.9696 0.8681 0.8415 0.7877 1 GNOMAD_G_SAS 0.35211268 UK10K=0.2512563,GNOMAD_G_AFR=0.04092638,GNOMAD_G_AMR=0.32059672,GNOMAD_G_NFE=0.27936247,GNOMAD_G_SAS=0.35211268 REMM 0.835447 CADD=0.6732617,REMM=0.835447
These are coming from datasets such as gnomAD and UK10K.
Could you please advise if I’m misinterpreting how the maxFrequency setting works, or if there's another parameter I should be adjusting to limit the output to more rare variants? (PS: I will try { maxFrequency: 0.01 and 0.1 } to run some test)
Thank you in advance.
HP.