To calculate the 95% CI for this estimate, we repeated the analysis, substituting in the upper and lower 95% CI’s for the expected number of damaging variants. More specifically, recall that we scaled the observed number of damaging variants in the 602 control trios (180) down to the expected number in 484 trios (180 * (484/602) = 145). Thus, we similarly estimated the upper limit of the expected number of damaging variants by determining the upper CI of the number of de novo damaging variants per child in the SSC (0.3443 variants per child) using the t.test function in R, and multiplying this estimate by 602 trios and rounding up. For example, we determined the upper estimate of the number of expected damaging variants as: expectedDamaging=celling(0.3443denovo variants per trio×602controls trios)=167
