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Table 1 Prevalence of heterozygous germline loss-of-function (LoF) variants identified in the BARD1 gene (transcript NM_000465.3) in controls and index patients with breast cancer (BC) or ovarian cancer (OC) according to family history and age at first diagnosis (AAD). A total of 26 heterozygous germline LoF variants were listed in the ExAC database (Exome Aggregation Consortium, non-Finnish Europeans (NFE); excluding The Cancer Genome Atlas data (TCGA); as of June 2016); 8 heterozygous germline LoF variants were listed in the FLOSSIES database (“Fabulous Ladies Over Seventy”; American-European ancestry); 2 heterozygous germline LoF variants were identified in geographically matched female controls (GMCs); 23 germline LoF variants were found in 4469 familial index patients with BC; no heterozygous germline LoF variant was found in 451 familial index patients with OC. Univariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When considering ExAC NFE nonTCGA controls only, ORs were similar to those given in Table 1 which consider all controls (AOR = 5.40, 95% CI = 3.08–9.47, P < 0.00001; BOR = 5.46, 95% CI = 3.02–9.88, P < 0.00001; COR = 5.13, 95% CI = 1.79–14.74, P = 0.01084; DOR = 12.16, 95% CI = 5.68–26.03, P < 0.00001; EOR = 7.51, 95% CI = 4.15–13.58, P < 0.00001; FOR = 5.58, 95% CI = 2.69–11.60, P = 0.00007; GOR = 2.74, 95% CI = 0.83–9.08, P = 0.11082; HOR = 2.32, 95% CI = 0.81–6.64, P = 0.11396, IOR = 1.58, 95% CI = 0.21–11.66, P = 0.47806)

From: Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer

Study sample Heterozygous carriers/number of tested individuals Carrier frequency (%) OR 95% CI P value (Fisher’s exact test)
ExAC NFE nonTCGA 26/27,173 0.10 / / /
FLOSSIES 8/7325 0.11 / / /
GMCs 2/2767 0.07 / / /
All controls 36/37,265 0.10 / / /
Familial BC index patients 23/4469 0.51 5.35A 3.17–9.04 < 0.00001
 Relative(s) with BC only 19/3651 0.52 5.41B 3.10–9.44 < 0.00001
 Relative(s) with OC 4/818 0.49 5.08C 1.81–14.31 0.01046
 AAD < 40 9/782 1.15 12.04D 5.78–25.08 < 0.00001
 AAD < 50 19/2662 0.71 7.43E 4.26–12.98 < 0.00001
 AAD 40–49 10/1880 0.53 5.53F 2.74–11.16 0.00005
 AAD 50–59 3/1145 0.26 2.72G 0.84–8.83 0.10969
 AAD ≥ 50 4/1807 0.22 2.29H 0.82–6.45 0.11217
 AAD ≥ 60 1/662 0.15 1.57I 0.21–11.43 0.47891
Familial OC index patients 0/451 / / / /
 Relative(s) with BC only 0/379 / / / /
 Relative(s) with OC 0/72 / / / /