Submissions for variant NM_000518.5(HBB):c.-81A>G

dbSNP: rs33981098

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000506722	SCV000601321	pathogenic	not provided	2017-04-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001255596	SCV001432104	pathogenic	Beta thalassemia intermedia	2022-11-23	criteria provided, single submitter	clinical testing	Variant summary: HBB c.-81A>G (also known as c. -31A>G) is located in the untranscribed region upstream of the HBB gene region. The variant was absent in 31390 control chromosomes (gnomAD). c.-81A>G has been reported in the literature in multiple individuals (mostly of Japanese origin) affected with Beta Thalassemia Intermedia (e.g. Takihara_1986, Hattori_1989, Ohba_1997, Fucharoen_1990). These data indicate that the variant is very likely to be associated with disease. In a functional assay, this variant resulted in reduced beta-globin RNA levels (Takihara_1986). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000506722	SCV001589195	pathogenic	not provided	2022-11-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant alters HBB gene expression (PMID: 3002527). ClinVar contains an entry for this variant (Variation ID: 15466). This variant is also known as -31A>G. This variant has been observed in individual(s) with beta thalassemia (PMID: 2634674, 3002527, 26029792). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the HBB gene. It does not change the encoded amino acid sequence of the HBB protein.
OMIM	RCV000016724	SCV000036994	pathogenic	Beta-plus-thalassemia	1989-01-01	no assertion criteria provided	literature only
GeneReviews	RCV000445643	SCV000537288	not provided	beta Thalassemia		no assertion provided	literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	RCV000445643	SCV001244529	pathogenic	beta Thalassemia	2019-11-25	no assertion criteria provided	curation
Natera, Inc.	RCV000445643	SCV002091632	pathogenic	beta Thalassemia	2017-03-17	no assertion criteria provided	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000445643	SCV002754540	pathogenic	beta Thalassemia	2022-05-11	no assertion criteria provided	clinical testing