rs4495487

badMag 3.5

This is a intron variant variant in the JAK2 gene.

Key Literature Trait Associations

Myeloproliferative Neoplasm Susceptibility

The A allele at rs4495487 tags the JAK2 46/1 (GGCC) haplotype, which confers a roughly 3-fold increased predisposition to JAK2 V617F-positive myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In a study of 1,753 MPN patients and 7,609 controls of European ancestry, the 46/1 haplotype was significantly enriched among V617F-positive cases (OR 3.10, P < 1×10⁻¹³).

Ohyashiki JH et al. “The C allele of JAK2 rs4495487 is an additional candidate locus that contributes to myeloproliferative neoplasm predisposition in the Japanese population.” Bmc Medical Genetics (2012)

Allele A

OR —

p —

N 245

Candidate gene study

Japanese

Bodemer C et al. “Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.” The Journal of Investigative Dermatology 130(3):804-815 (2010)

Allele A

OR 3.10

p 1.0e-13

Large GWAS

Li SL et al. “The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies.” Annals of Hematology (2014)

Allele A

OR 2.19

p 1.0e-20

N 15,995

Large GWAS

multi-ancestry

Budd-Chiari Syndrome

The CC genotype of rs4495487 was associated with markedly elevated risk of Budd-Chiari syndrome (BCS) — hepatic vein thrombosis often driven by underlying JAK2 V617F-positive MPN — in a Chinese case-control study. Among JAK2 V617F-positive BCS patients, the CC genotype conferred an OR of 13.60 (95% CI 2.04–90.79) versus TT, and OR 4.44 (95% CI 1.31–15.12) for combined-type BCS in a recessive model. This association likely reflects the role of the 46/1 haplotype in predisposing to JAK2 V617F acquisition, which in turn promotes thrombotic complications including BCS. The wide confidence intervals and single-study origin limit confidence.

Zhang P et al. “Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China.” Gastroenterology Research and Practice (2015)

Allele C

OR 13.60

p 1.0e-2

N 611

Preliminary work

Chinese

▶

ClinVar annotation

Benign★☆☆☆

1 submitter

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Loading comments…