d was estimated as the number of damaging variants observed (199) minus the expected number of damaging variants, where the expected number of variants was estimated from the SSC control trios. More specifically, we scaled the observed number of damaging variants in the 602 control trios (180) to the expected number in 484 trios (180 *(484/602) = 145). Therefore, we estimated d as 199−145 = 54.