Rare and putatively damaging germ line NBN variants identified in patients with B-ALL (NBN NM_002485)
| Variant ID . | Exon . | Class . | Genomic location . | Sequence variant . | AF . | CADD . | REVEL . | Designation∗ . | Cases . | Genetic ancestry group (cases) . |
|---|---|---|---|---|---|---|---|---|---|---|
| p.L4P | 1 | Missense | 8-90996779-A-G | c.T11C | 0 | 24.6 | 0.462 | VUS | 2 | AMR (2) |
| p.L18I | 2 | Missense | 8-90995069-G-T | c.C52A | 1.41E−05 | 24 | 0.158 | VUS | 1 | AFR (1) |
| p.Q39K | 2 | Missense | 8-90995006-G-T | c.C115A | 0 | 24 | 0.542 | VUS | 1 | AMR (1) |
| p.S40L | 2 | Missense | 8-90995002-G-A | c.C119T | 1.19E−05 | 27 | 0.88 | VUS | 2 | EUR (2) |
| p.S93L | 3 | Missense | 8-90993645-G-A | c.C278T | 5.81E−04 | 25 | 0.457 | VUS† | 2 | EUR (2) |
| p.M152I | 4 | Missense | 8-90992986-C-T | c.G456A | 1.13E−04 | 27.3 | 0.482 | VUS† | 7 | EUR (4), AMR (2), Other (1) |
| p.K156N | 4 | Missense | 8-90992974-T-G | c.A468C | 1.51E−04 | 26.1 | 0.438 | VUS† | 3 | AMR (3) |
| p.E179K | 5 | Missense | 8-90990497-C-T | c.G535A | 3.98E−06 | 32 | 0.308 | VUS | 1 | EUR (1) |
| p.V184A | 5 | Missense | 8-90990481-A-G | c.T551C | 0 | 25.2 | 0.179 | VUS | 1 | Other (1) |
| p.E217Q | 6 | Missense | 8-90983454-C-G | c.G649C | 7.97E−06 | 25.1 | 0.224 | VUS | 1 | EUR (1) |
| p.K219fs | 6 | Frameshift | 8-90983441-ATTTGT-A | c.657_661del | 2.02E−04 | 32 | NA | Pathogenic | 7 | EUR (5), AMR (2) |
| p.F222L | 6 | Missense | 8-90983439-A-G | c.T664C | 1.77E−05 | 28.2 | 0.937 | VUS | 1 | EUR (1) |
| p.I228R | 6 | Missense | 8-90983420-A-C | c.T683G | 7.10E−05 | 25.7 | 0.54 | VUS | 3 | EUR (2), AFR (1) |
| p.A241T | 7 | Missense | 8-90982767-C-T | c.G721A | 1.59E−05 | 26 | 0.396 | VUS | 1 | AMR (1) |
| p.F263S | 7 | Missense | 8-90982700-A-G | c.T788C | 1.95E−04 | 25.4 | 0.737 | VUS† | 2 | AFR (1), Other (1) |
| p.G274R | 7 | Missense | 8-90982668-C-T | c.G820A | 7.96E−06 | 24 | 0.308 | VUS | 1 | AFR (1) |
| p.L281X | 7 | Stop gain | 8-90982646-A-C | c.T842G | 3.98E−06 | 33 | NA | Pathogenic | 1 | AMR (1) |
| p.A313V | 8 | Missense | 8-90976694-G-A | c.C938T | 3.18E−05 | 26.8 | 0.661 | VUS | 1 | AMR (1) |
| p.Q448L | 10 | Missense | 8-90967565-T-A | c.A1343T | 4.25E−05 | 21.5 | 0.037 | VUS† | 1 | AFR (1) |
| p.D469Y | 11 | Missense | 8-90965912-C-A | c.G1405T | 6.16E−05 | 26.1 | 0.149 | VUS† | 1 | AFR (1) |
| p.P495L | 11 | Missense | 8-90965833-G-A | c.C1484T | 3.19E−05 | 23.9 | 0.097 | VUS | 1 | EUR (1) |
| p.E552Q | 11 | Missense | 8-90965663-C-G | c.G1654C | 0 | 23.6 | 0.058 | VUS | 1 | EUR (1) |
| p.V556E | 11 | Missense | 8-90965650-A-T | c.T1667A | 1.99E−05 | 22.5 | 0.078 | VUS | 2 | EUR (2) |
| p.E564K | 11 | Missense | 8-90965627-C-T | c.G1690A | 8.10E−04 | 22.9 | 0.081 | (Likely) Benign | 5 | EUR (1), EAS (2), SAS (1), Other (1) |
| p.S706X | 14 | Stop gain | 8-90955548-G-C | c.C2117G | 1.06E−05 | 42 | NA | Pathogenic | 1 | EUR (1) |
| Variant ID . | Exon . | Class . | Genomic location . | Sequence variant . | AF . | CADD . | REVEL . | Designation∗ . | Cases . | Genetic ancestry group (cases) . |
|---|---|---|---|---|---|---|---|---|---|---|
| p.L4P | 1 | Missense | 8-90996779-A-G | c.T11C | 0 | 24.6 | 0.462 | VUS | 2 | AMR (2) |
| p.L18I | 2 | Missense | 8-90995069-G-T | c.C52A | 1.41E−05 | 24 | 0.158 | VUS | 1 | AFR (1) |
| p.Q39K | 2 | Missense | 8-90995006-G-T | c.C115A | 0 | 24 | 0.542 | VUS | 1 | AMR (1) |
| p.S40L | 2 | Missense | 8-90995002-G-A | c.C119T | 1.19E−05 | 27 | 0.88 | VUS | 2 | EUR (2) |
| p.S93L | 3 | Missense | 8-90993645-G-A | c.C278T | 5.81E−04 | 25 | 0.457 | VUS† | 2 | EUR (2) |
| p.M152I | 4 | Missense | 8-90992986-C-T | c.G456A | 1.13E−04 | 27.3 | 0.482 | VUS† | 7 | EUR (4), AMR (2), Other (1) |
| p.K156N | 4 | Missense | 8-90992974-T-G | c.A468C | 1.51E−04 | 26.1 | 0.438 | VUS† | 3 | AMR (3) |
| p.E179K | 5 | Missense | 8-90990497-C-T | c.G535A | 3.98E−06 | 32 | 0.308 | VUS | 1 | EUR (1) |
| p.V184A | 5 | Missense | 8-90990481-A-G | c.T551C | 0 | 25.2 | 0.179 | VUS | 1 | Other (1) |
| p.E217Q | 6 | Missense | 8-90983454-C-G | c.G649C | 7.97E−06 | 25.1 | 0.224 | VUS | 1 | EUR (1) |
| p.K219fs | 6 | Frameshift | 8-90983441-ATTTGT-A | c.657_661del | 2.02E−04 | 32 | NA | Pathogenic | 7 | EUR (5), AMR (2) |
| p.F222L | 6 | Missense | 8-90983439-A-G | c.T664C | 1.77E−05 | 28.2 | 0.937 | VUS | 1 | EUR (1) |
| p.I228R | 6 | Missense | 8-90983420-A-C | c.T683G | 7.10E−05 | 25.7 | 0.54 | VUS | 3 | EUR (2), AFR (1) |
| p.A241T | 7 | Missense | 8-90982767-C-T | c.G721A | 1.59E−05 | 26 | 0.396 | VUS | 1 | AMR (1) |
| p.F263S | 7 | Missense | 8-90982700-A-G | c.T788C | 1.95E−04 | 25.4 | 0.737 | VUS† | 2 | AFR (1), Other (1) |
| p.G274R | 7 | Missense | 8-90982668-C-T | c.G820A | 7.96E−06 | 24 | 0.308 | VUS | 1 | AFR (1) |
| p.L281X | 7 | Stop gain | 8-90982646-A-C | c.T842G | 3.98E−06 | 33 | NA | Pathogenic | 1 | AMR (1) |
| p.A313V | 8 | Missense | 8-90976694-G-A | c.C938T | 3.18E−05 | 26.8 | 0.661 | VUS | 1 | AMR (1) |
| p.Q448L | 10 | Missense | 8-90967565-T-A | c.A1343T | 4.25E−05 | 21.5 | 0.037 | VUS† | 1 | AFR (1) |
| p.D469Y | 11 | Missense | 8-90965912-C-A | c.G1405T | 6.16E−05 | 26.1 | 0.149 | VUS† | 1 | AFR (1) |
| p.P495L | 11 | Missense | 8-90965833-G-A | c.C1484T | 3.19E−05 | 23.9 | 0.097 | VUS | 1 | EUR (1) |
| p.E552Q | 11 | Missense | 8-90965663-C-G | c.G1654C | 0 | 23.6 | 0.058 | VUS | 1 | EUR (1) |
| p.V556E | 11 | Missense | 8-90965650-A-T | c.T1667A | 1.99E−05 | 22.5 | 0.078 | VUS | 2 | EUR (2) |
| p.E564K | 11 | Missense | 8-90965627-C-T | c.G1690A | 8.10E−04 | 22.9 | 0.081 | (Likely) Benign | 5 | EUR (1), EAS (2), SAS (1), Other (1) |
| p.S706X | 14 | Stop gain | 8-90955548-G-C | c.C2117G | 1.06E−05 | 42 | NA | Pathogenic | 1 | EUR (1) |
AF, allele frequency in gnomAD; AFR, African/African American; AMR, admixed American; CADD, Combined Annotation Dependent Depletion; EAS, East Asian; EUR, European (non-Finnish); SAS, South Asian; VUS, variant of uncertain significance.
NBN variant designation reported in the ClinVar database (accession date: March 2023).
VUS with conflicting interpretations of pathogenicity.