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. 2017 Jun 20;24(8):427–443. doi: 10.1530/ERC-17-0196

Table 3.

Association between seven heterozygous missense variants in six candidate genes and small intestinal neuroendocrine tumors (SI-NETs).

Variant effect prediction Minor allele frequency (MAF) in control cohorts MAF in germline of SI-NET patients compared to the EpiHealth (two-tailed Fisher’s exact test)e MAF in germline and/or tumor of SI-NET patients compared to the EpiHealth (two-tailed Fisher’s exact test)e
rsID Gene cDNA Amino acid residue change SIFT Polyphen Mut.Taster 1000G (EUR) MAFa Exac 0.3 (EUR) MAFb EpiHealth controls MAFc,d SI-NETs MAF (germline)c OR 95% CI P-Value SI-NETs MAF (cancer+germline)c OR 95% CI P-Value
rs61748181 TERT C/T p.(Ala279Thr) Tolerated Probably damaging Disease causing 0.036 0.05 0.036 (167/4636) 0.028 (9/316) 0.76 0.35–1.55 0.64 0.027 (12/444) 0.74 0.37–1.35 0.42
rs34635677 SDHA A/T p.(Asp38Val) Tolerated Benign Polymorphism 0.032 0.044 0.034 (157/4636) 0.032 (10/316) 0.93 0.43–1.78 1 0.035 (16/458) 1 0.57–1.75 0.89
rs33927012 SDHB T/C p.(Ser163Pro) Tolerated Benign Disease causing 0.017 0.015 0.02 (96/4636) 0.013 (4/316) 0.6 0.16–1.62 0.41 0.011 (5/460) 0.52 0.16–1.26 0.22
rs11214077 SDHD A/G p.(His50Arg) Tolerated Probably damaging Disease causing 0.017 0.01 0.01 (46/4636) 0.013 (4/318) 1.27 0.33–3.51 0.56 0.011 (5/460) 1.1 0.34–2.77 0.8
rs34677591 SDHD G/A p.(Gly12Ser) Tolerated Benign Disease causing 0.01 0.01 0.008 (36/4636) 0.009 (3/318) 1.22 0.24–3.88 0.74 0.007 (3/460) 0.84 0.16–2.67 1
rs36053993 MUTYH G/A p.(Gly396Asp) Damaging Probably damaging Disease causing 0.009 0.004 0.003 (12/4636) 0.016 (5/316) 6.19 1.7–19.02 0.0034 0.013 (6/460) 5.09 1.56–14.74 0.0038
rs104893751 OGG1 G/A p.(Arg46Gln) Damaging Probably damaging Disease causing 0.002 0.003 0.005 (22/4636) 0.01 (3/314) 2.02 0.39–6.79 0.2 0.009 (4/460) 1.84 0.46–5.45 0.29
a

Allele frequencies in this column are based on the European (Non-Finnish) fraction of the 1000 Genomes project, consisting of 503 subjects; ballele frequencies in this column are based on the European (Non-Finnish) fraction of the Exac Aggregation Project, consisting of 33,370 subjects; cminor allele frequencies (MAFs) were calculated for control and case cohorts by dividing the the number of minor alleles detected by all possible alleles in the population tested. These numbers are reported in parenthesis under the MAFs. The numbers for patients affected with the disease include 15 families, counted as one subject per family affected with SI-NET. Thus, the familial cases add a maximum of 30 alleles to the calculations of MAF in the cohort of patients affected with SI-NETs; dthe control cohort used for calculations was the Swedish EpiHealth study; composed of 2318 individuals with the same genetic background as the affected subjects; evariants were tested for statistical significance by comparing their prevalence in germline or in germline and/or tumor of affected subjects to their frequency in the EpiHealth. Subjects diagnosed with any typer of cancer were excluded from the EpiHealth cohort before analysis. A two-tailed Fisher’s exact test was used on 2 × 2 contingency tables containing allele MAFs of cases and controls to obtain odds ratios (ORs), 95% confidence intervals (CIs) and P values for each comparison. No correction for multiple testing has been done, since only one test was significant (p.(Gly396Asp) in MUTYH and the P value was very small.