Figure 1

Selection of variants based on allele frequency and predicted effect on the translated protein. (a) The initial informatics analysis resulted in an average of ~13,000 variants per person in Bin 1 genes, ~175,000 variants per person in Bin 2b genes, and ~9,000 variants per person in Bin 2c genes. (b) Limiting these variants to <5% allele frequency (AF) or <1% AF reduces these counts ~10–15 fold. (c) Restricting to protein-coding variants (missense, nonsense, frameshift, and splice-site) at <5% AF results in ~10 variants per person in Bin 1 genes and 100–200 variants per person in Bin 2b genes. At <1% AF there were ~5 variants per person in Bin 1 genes and 50–100 variants per person in Bin 2b genes. (d) Restricting only to truncating variants (nonsense, frameshift, and splice-site) results in only a small number of variants to be analyzed by the reviewer. Of note, the AF cut-off (<5 vs. <1%) does not dramatically affect the number of truncating variants that are selected.