On the other hand, the empirically determined allele frequency thresholds derived by combining older ATM, BRCA1, BRCA2, and CHEK2 case-control mutation screening data with EVS and 1000G data - found to be 0.1% for the three genes (ATM, BRCA1, and BRCA2) where inheritance of biallelic mutations is either embryonic lethal or causes a developmental phenotype that severely reduces reproductive fitness, and 0.32% for CHEK2 - provides a new tool to help with evaluation of the many rare variants observed in a case-control mutation screening study of candidate cancer susceptibility genes. This evidence concerns the gene BRCA1 and cancer.