rs6897932

plus

Geno	Mag	Summary
(C;C)	2	1.08x increased risk for multiple sclerosis
(C;T)	1.8	0.91x decreased risk for multiple sclerosis
(T;T)	2.1	0.70x decreased risk for multiple sclerosis

Reference

GRCh38 38.1/141

Chromosome

5

Position

35874473

Gene

IL7R

is a	snp
is	mentioned by
dbSNP	rs6897932
dbSNP (classic)	rs6897932
ClinGen	rs6897932
ebi	rs6897932
HLI	rs6897932
Exac	rs6897932
Gnomad	rs6897932
Varsome	rs6897932
LitVar	rs6897932
Map	rs6897932
PheGenI	rs6897932
Biobank	rs6897932
1000 genomes	rs6897932
hgdp	rs6897932
ensembl	rs6897932
geneview	rs6897932
scholar	rs6897932
google	rs6897932
pharmgkb	rs6897932
gwascentral	rs6897932
openSNP	rs6897932
23andMe	rs6897932
SNPshot	rs6897932
SNPdbe	rs6897932
MSV3d	rs6897932
GWAS Ctlg	rs6897932

GMAF

0.191

Max Magnitude

2.1

?

(C;C) (C;T) (T;T)

28

The (C) allele of rs6897932, located in the alternatively spliced exon 6 of IL7RA gene and encoding the amino acid threonine rather than isoleucine at amino acid position 244, is associated with a slight increase (18%) in risk of developing multiple sclerosis. [PMID 17660817; Nature Genetics 39, 1083 - 1091 (2007) SG Gregory et al.]

Note that the (C) allele is the most common at this position in all known populations and influences the ratios of the alternative isoforms (membrane bound and soluble) of the gene. Thus, we consider the (T) allele protective.

blog post giving perspective on the significance of this snp

[PMID 17660817] a significant risk factor for multiple sclerosis in four independent (overall P = 2.9 x 10(-7)) influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.

nejm C allele increasing the risk of multiple sclerosis (odds ratio, approximately 1.2)

[PMID 18721276] A replication case-control study involving 599 Spanish patients with multiple sclerosis yielded a per allele odds ratio of 1.32 per rs6897932(C), (CI: 1.1-1.6, p = 0.0031), and odds per (C;C) genotype vs (T;T) and (C;T) genotypes of 1.5 (CI: 1.18-1.87, p = 0.0007).

GWAS
SNP	rs6897932
PubMedID	[PMID 17660530]
Condition	Multiple sclerosis
Gene	IL7RA
Risk Allele	C
pValue	3.00E-007
OR	1.18
95% CI	1.11-1.26

GWAS snp
PMID	[PMID 17554260 ]
Trait	Type 1 diabetes
Title	Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Risk Allele	G
P-val	0.0000079999999999999996
Odds Ratio	1.12 [1.06-1.19]

GWAS snp
PMID	[PMID 19525953 ]
Trait	Multiple sclerosis
Title	Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci
Risk Allele	C
P-val	0.000002
Odds Ratio	1.12 [1.02-1.23]

OMIM	612595
Desc	MULTIPLE SCLEROSIS, SUSCEPTIBILITY TO, 3; MS3
Variant
Related	also

[PMID 19626041] Variation in IL7R predisposes to sarcoid inflammation

[PMID 19744146] IL7RA polymorphisms and chronic inflammatory arthropathies

[PMID 18650830] Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians

[PMID 20112030 ] Genetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility

[PMID 20952449] Evaluation of the established non-MHC multiple sclerosis loci in an Indian population

[PMID 21287555] The interleukin-7 receptor ? chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis

[PMID 21543551] Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis

[PMID 22363405 ] Sample Reproducibility of Genetic Association Using Different Multimarker TDTs in Genome-Wide Association Studies: Characterization and a New Approach

[PMID 17915034 ] Finding disease candidate genes by liquid association.

[PMID 18354419] IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations.

[PMID 18461312] The immunogenetics of multiple sclerosis.

[PMID 18490360 ] The complex genetics of multiple sclerosis: pitfalls and prospects.

[PMID 18563381] Study of the association between the CAPSL-IL7R locus and type 1 diabetes.

[PMID 18565446 ] Refining genetic associations in multiple sclerosis.

[PMID 18853133 ] Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.

[PMID 19073967 ] Shared and distinct genetic variants in type 1 diabetes and celiac disease.

[PMID 19221116 ] Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS.

[PMID 19231135] Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients.

[PMID 19293837 ] Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor.

[PMID 19359276 ] Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes.

[PMID 19468064 ] Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions.

[PMID 19546505 ] IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H).

[PMID 19626040 ] Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis.

[PMID 19956108 ] Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3-q14.1.

[PMID 20007504 ] Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci.

[PMID 20072139 ] Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis.

[PMID 20182566 ] The genetic aspects of multiple sclerosis.

[PMID 20194581] Interleukin 7 receptor alpha polymorphism rs6897932 and susceptibility to multiple sclerosis in the Western Balkans.

[PMID 20368992 ] Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients.

[PMID 20405052 ] The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.

[PMID 21161391] Association between the IL7R T244I polymorphism and multiple sclerosis: a meta-analysis.

[PMID 21244681 ] Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma.

[PMID 21875636 ] Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination.

[PMID 21911588] IL2RA gene polymorphism rs2104286 A>G seen in multiple sclerosis is associated with intermediate uveitis: possible parallel pathways?

[PMID 22262655] The IL-7Ralpha pathway is quantitatively and functionally altered in CD8 T cells in multiple sclerosis.

GWAS snp
PMID	[PMID 21833088 ]
Trait	Multiple sclerosis
Title	Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
Risk Allele	G
P-val	2E-8
Odds Ratio	1.11 [1.09-1.13]

[PMID 24166352] The Promoter SNP, but not the Alternative Splicing SNP, is Linked to Multiple Sclerosis Among Jordanian Patients

[PMID 24242875] Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus

[PMID 24337176] Association analysis of IL7R polymorphisms with inflammatory demyelinating diseases

[PMID 24357513] The variant interleukin 1f7 rs3811047 G>A was associated with a decreased risk of gastric cardiac adenocarcinoma in a Chinese Han population

[PMID 22492128] Association of SNPs rs6498169 and rs10984447 with multiple sclerosis in Saudi patients: a model of the usefulness of familial aggregates in identifying genetic linkage in a multifactorial disease.

[PMID 23454692 ] Concentration and activity of the soluble form of the interleukin-7 receptor alpha in type 1 diabetes identifies an interplay between hyperglycemia and immune function.

[PMID 23462217] Polymorphisms in the interleukin-7 receptor alpha gene and mortality in untreated HIV-infected individuals.

[PMID 23692589 ] Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor.

ClinVar
Risk	Rs6897932(T;T)
Alt	Rs6897932(T;T)
Reference	Rs6897932(C;C)
Significance	Non-pathogenic
Disease	not specified Severe Combined Immune Deficiency
Variation	info
Gene	IL7R
CLNDBN	not specified Severe Combined Immune Deficiency
Reversed	0
HGVS	NC_000005.9:g.35874575C>T
CLNSRC	ClinVar
CLNACC	RCV000121219.2, RCV000267316.1,

[PMID 25903732] Genetic variants in interleukin 7 receptor α chain (IL-7Ra) are associated with multiple sclerosis risk and disability progression in Central European Slovak population

[PMID 27456877] Interleukin 7 receptor polymorphisms and the risk of multiple sclerosis: A meta-analysis.

[PMID 28863969] Soluble Interleukin-7 receptor levels and risk of acute graft-versus-disease after allogeneic haematopoietic stem cell transplantation.

[PMID 29456530 ] Donor Genotype in the Interleukin-7 Receptor α-Chain Predicts Risk of Graft-versus-Host Disease and Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation.

[PMID 30069682] Association of interleukin 6, interleukin 7 receptor alpha, and interleukin 12B gene polymorphisms with multiple sclerosis.

[PMID 31929513] IL7RA genetic variants differentially affect IL-7Rα expression and alternative splicing: a role in autoimmune and infectious diseases?

[PMID 32683075] Candidate Gene Association Analysis of Multiple Sclerosis in the Jordanian Arab Population: A Case-Control Study.

[PMID 33348212] Association between IL7 Receptor Alpha (Il7ra) gene rs6897932 polymorphism and the risk of Multiple Sclerosis: A meta-regression and meta-analysis.

[PMID 33568552 ] U2AF2 binds IL7R exon 6 ectopically and represses its inclusion.