We recently published a paper on a novel methodology called CRAFTS-indels (Calculating Regional Allele Frequency Targeting Small indels), an innovative algorithm that combines the allele frequencies of distinct indels within a genomic region to provide a “regional allele frequency” or rAF.
By comparing rAF to standard allele frequency across large datasets like gnomAD, an internal cohort, and UK Biobank, we discovered that a substantial proportion of rare indels (22% in gnomAD) had an unexpectedly high rAF despite having a low standard frequency. Analysis of the overlap of regions based on their rAF with low complexity regions and with ClinVar classification supported the pertinence of rAF. Using the internal dataset, we illustrated the utility of CRAFTS-indel in the analysis of de novo variants and the potential negative impact of rAF-hi indels in gene discovery.
We believe rAF annotation will be a great addition as an annotation for the gnomAD dataset, would be very valuable for researchers and potentially clinical geneticists.
Here is the link to the paper: Functional & Integrative Genomics Journal (Link: Assisting the analysis of insertions and deletions using regional allele frequencies).
Thanks
Sarath Babu