rs1800057

badMag 4.0

This is a variant in the ATM gene that changes a proline to an arginine.

Key Literature Trait Associations

Myeloproliferative neoplasms

The G allele of rs1800057 in ATM is associated with increased risk of myeloproliferative neoplasms (MPNs), a group of clonal hematopoietic stem cell disorders. A large GWAS (PMID 33057200) combining UK Biobank and FinnGen data (approximately 1,726 cases and over 583,000 controls) reported OR 1.65 (95% CI 1.41–1.92, P=2×10⁻¹⁰) at genome-wide significance. This relatively large effect size for a common cancer locus is consistent with ATM's known role in maintaining hematopoietic stem cell genomic integrity.

Bao EL et al. “Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells.” Nature 586(7831):769-775 (2020)
Allele G
OR 1.65
p 2.0e-10
N 585,140
Large GWAS
European

Prostate cancer

The rs1800057 G allele in ATM is associated with increased prostate cancer risk. A large GWAS consortium meta-analysis of more than 140,000 men (PMID 29892016) identified rs1800057-G as a susceptibility locus with OR 1.16 (95% CI 1.10–1.22, P=8×10⁻⁹), meeting genome-wide significance. This finding is consistent with ATM's established role as a DNA repair gene frequently mutated in aggressive prostate cancers, and highlights rs1800057 as a low-penetrance germline risk allele.

Schumacher FR et al. “Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.” Nature Genetics 50(7):928-936 (2018)
Allele G
OR 1.16
p 8.0e-9
N 140,254
Large GWAS
European
Qian D et al. “A pleiotropic ATM variant (rs1800057 C>G) is associated with risk of multiple cancers.” Carcinogenesis (2022)
Allele G
OR —
p 5.3e-7
Preliminary work
multi-ancestry

Uterine leiomyoma

The G allele of rs1800057 in ATM is associated with increased risk of uterine leiomyoma (fibroids). A large GWAS of 16,595 cases and 523,330 controls of European ancestry (PMID 30194396) identified rs1800057-G with OR 1.28 (95% CI 1.19–1.38, P=3×10⁻¹¹), reaching genome-wide significance. This association highlights shared genetic architecture between benign uterine tumors and malignant cancer susceptibility loci, consistent with the pleiotropic role of ATM in DNA damage response across different tissue types.

Rafnar T et al. “Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.” Nature Communications 9(1):3636 (2018)
Allele G
OR 1.28
p 3.0e-11
N 539,925
Large GWAS
European

Renal cell carcinoma

The rs1800057 G allele in ATM is associated with elevated risk of renal cell carcinoma. A multi-stage GWAS meta-analysis (PMID 28598434) including 10,784 cases and 20,406 discovery controls with European ancestry reported OR 1.38 (95% CI 1.23–1.53, P=9×10⁻⁹) at genome-wide significance. The cross-cancer pleiotropy of rs1800057, as confirmed by Qian et al. (2022), supports a shared ATM-mediated susceptibility mechanism across renal and other solid tumor types.

Scelo G et al. “Genome-wide association study identifies multiple risk loci for renal cell carcinoma.” Nature Communications 8:15724 (2017)
Allele G
OR 1.38
p 9.0e-9
N 40,373
Large GWAS
European
Qian D et al. “A pleiotropic ATM variant (rs1800057 C>G) is associated with risk of multiple cancers.” Carcinogenesis (2022)
Allele G
OR —
p 5.3e-7
Preliminary work
multi-ancestry

Breast Cancer Risk

The G allele of rs1800057 (ATM p.Pro1054Arg) is associated with a modest but statistically significant increase in breast cancer risk. A large pooled analysis of 26,101 cases and 29,842 controls across 23 studies (PMID 20826828) found an overall trend OR of 1.06 (P=0.04) for ATM missense variants including P1054R, with a stronger signal among bilateral and familial cases (OR 1.12, 95% CI 1.02–1.23). The variant is rare (~2% frequency in Europeans), limiting its population-attributable risk, but its presence in ATM—a key DNA damage response gene—gives it biological plausibility as a low-penetrance cancer susceptibility allele.

Fletcher O et al. “Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls.” Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology (2010)
Allele G
OR 1.06
p 4.0e-2
N 55,943
Preliminary work
multi-ancestry
Qian D et al. “A pleiotropic ATM variant (rs1800057 C>G) is associated with risk of multiple cancers.” Carcinogenesis (2022)
Allele G
OR —
p 5.3e-7
Preliminary work
multi-ancestry
▶

GWAS Catalog Trait Associations (6)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

blood protein amount

Gudjonsson A et al. “A genome-wide association study of serum proteins reveals shared loci with common diseases.” Nature Communications 13(1):480 (2022)
Allele G
OR 1.82
p 9.0e-168
N 5,354
Large GWAS
European

uterine fibroid

Rafnar T et al. “Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.” Nature Communications 9(1):3636 (2018)
Allele G
OR 1.28
p 3.0e-11
N 539,925
Large GWAS
European

myeloproliferative disorder

Bao EL et al. “Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells.” Nature 586(7831):769-775 (2020)
Allele G
OR 1.65
p 2.0e-10
N 585,140
Large GWAS
European

mean reticulocyte volume

Vuckovic D et al. “The Polygenic and Monogenic Basis of Blood Traits and Diseases.” Cell 182(5):1214-1231.e11 (2020)
Allele G
OR 0.04
p 3.0e-9
N 408,112
Large GWAS
European

prostate carcinoma

Schumacher FR et al. “Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.” Nature Genetics 50(7):928-936 (2018)
Allele G
OR 1.16
p 8.0e-9
N 140,254
Large GWAS
European

renal cell carcinoma

Scelo G et al. “Genome-wide association study identifies multiple risk loci for renal cell carcinoma.” Nature Communications 8:15724 (2017)
Allele G
OR 1.38
p 9.0e-9
N 31,190
Large GWAS
European
▶

ClinVar annotation

Likely Benign★★★☆
5 submitters42 publications

Ataxia-telangiectasia syndrome (AT); Carcinoma of colon (CRC); Familial cancer of breast; Hereditary breast ovarian cancer syndrome; Hereditary cancer-predisposing syndrome; not specified

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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