rs6939340

Orientation

plus

Stabilized

plus

Geno	Mag	Summary
(A;A)	0	normal
(A;G)		1.42x possible increased risk for neuroblastoma
(G;G)		2x increased risk for neuroblastoma

Reference

GRCh38 38.1/141

Chromosome

6

Position

22139775

Gene	CASC15, NBAT1

is a	snp
is	mentioned by
dbSNP	rs6939340
dbSNP (classic)	rs6939340
ClinGen	rs6939340
ebi	rs6939340
HLI	rs6939340
Exac	rs6939340
Gnomad	rs6939340
Varsome	rs6939340
LitVar	rs6939340
Map	rs6939340
PheGenI	rs6939340
Biobank	rs6939340
1000 genomes	rs6939340
hgdp	rs6939340
ensembl	rs6939340
geneview	rs6939340
scholar	rs6939340
google	rs6939340
pharmgkb	rs6939340
gwascentral	rs6939340
openSNP	rs6939340
23andMe	rs6939340
SNPshot	rs6939340
SNPdbe	rs6939340
MSV3d	rs6939340
GWAS Ctlg	rs6939340

GMAF

0.3471

Max Magnitude

0

?	(A;A) (A;G) (G;G)	28

SNPs clustered in one region of chromosome 6p22 have been linked to increased risk for the exceedingly rare childhood cancer known as neuroblastoma. A study involving 720 patients determined that rs6939340(G;G) genotypes had increased likelihood of neuroblastoma development (odds ratio 1.97, CI: 1.58 to 2.45, p=9.3 x 10^-15). At-risk homozygotes diagnosed with neuroblastoma had, on average, more malignant clinical presentation, more aggressive disease, and poorer long-term survival.[PMID 18463370]

Presumably driven primarily by the at-risk homozygotes, the rs6939340(G) allele was considered to be a risk factor, however, there was insufficient data to conclude whether rs6939340(A;G) heterozygotes were actually at any increased risk compared to rs6939340(A;A) "wild-type" homozygotes.[PMID 18463370]

Note that this is an excellent example for putting SNP-associated risks in a relative context of Lifetime Risk. The annual mortality rate for neuroblastoma for everyone combined is 10 per 1 million children in the 0- to 4-year-old age group. Assuming the ~20% of children with the most "at-risk" genotype identified to date, i.e. rs6939340(G;G) homozygotes, have double the risk of the other genotypes, which means their mortality risk has only gone up to ~17 per million, versus the risk for the 80% of individuals with other genotypes going down to ~9 per million. Even if these studies are successfully replicated, odds of 17 out of a million are very very small, so these studies are not useful in predicting disease, even if they may ultimately have benefit in the management of individuals diagnosed with disease.

GWAS
SNP	rs6939340
PubMedID	[PMID 18463370]
Condition	Neuroblastoma
Gene	FLJ22536, FLJ44180
Risk Allele	G
pValue	9.00E-015
OR	1.37
95% CI	1.27-1.49

OMIM	256700
Desc	NEUROBLASTOMA
Variant
Related	also

OMIM	613015
Desc
Variant
Related	also

[PMID 19412175] Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.