Submissions for variant NM_000518.5(HBB):c.315+1G>T

dbSNP: rs33945777

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759065	SCV000888147	pathogenic	not provided	2017-12-05	criteria provided, single submitter	clinical testing	The HBB c.315+1G>T variant (also known as IVS-II-1 (G>T)) disrupts a canonical splice-donor site and interferes with normal HBB mRNA splicing. The frequency of this variant in the general population, 0.0000066 (1/152150 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with beta-thalassemia (PMID: 3828533 (1987), PMID: 20524821 (2010)). Based on the available information, this variant is classified as pathogenic.
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV001170018	SCV001251692	pathogenic	beta Thalassemia	2020-05-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001170018	SCV001363911	pathogenic	beta Thalassemia	2019-02-12	criteria provided, single submitter	clinical testing	Variant summary: HBB c.315+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 276896 control chromosomes. c.315+1G>T has been reported in the literature in individuals affected with Beta Thalassemia. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000759065	SCV002049972	pathogenic	not provided	2021-07-10	criteria provided, single submitter	clinical testing	The HBB c.315+1G>T variant (rs33945777), also known as IVS II-1 (G>T), is reported in the literature in individuals affected with beta(0) thalassemia (see HbVar, Broquere 2010, Chehab 1987). This variant is reported in ClinVar (Variation ID: 619686). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 2, which is likely to negatively impact gene function. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database for c.315+1G>T: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=2602&.cgifields=histD Broquere C et al. Phenotypic expression and origin of the rare beta-thalassemia splice site mutation HBB:c.315 + 1G>T. Hemoglobin. 2010 Jun;34(3):322-6. Chehab FF et al. The molecular basis of beta-thalassemia in Lebanon: application to prenatal diagnosis. Blood. 1987 Apr;69(4):1141-5.