ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.92+5G>T (rs33915217)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000030005 SCV000052660 pathogenic Beta thalassemia major 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505898 SCV000601329 pathogenic not provided 2016-09-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506613 SCV000603942 pathogenic not specified 2018-08-06 criteria provided, single submitter clinical testing The HBB c.92+5G>T variant (rs33915217), also known as IVS-I-5 (G->T), has been reported in multiple patients with severe beta(+) thalassemia (Atweh 1987, HbVar database and references therein). Functional studies indicate that the variant causes aberrant splicing of the HBB RNA and reduction of full-length mRNA transcripts (Atweh 1987). The variant is listed as pathogenic in ClinVar (Variation ID: 15448), and observed once in the Genome Aggregation Database (1/245966 alleles). Computational algorithms (GeneSplicer, Human Splicing Finder, MaxEntScan, MutationTaster, NetGene2, NNSplice, SpliceSiteFinder-like) predict that the variant reduces the efficiency of the nearby canonical splice donor, consistent with functional studies. Based on the above information, the variant is classified as pathogenic. References: Link to HbVar database for IVS-I-5 (G->T): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=825 Atweh G et al. A new mutation in IVS-1 of the human beta globin gene causing beta thalassemia due to abnormal splicing. Blood. 1987; 70(1):147-51.
OMIM RCV000016706 SCV000036976 pathogenic Beta-plus-thalassemia 1989-03-01 no assertion criteria provided literature only
Counsyl RCV000984182 SCV001132216 pathogenic beta Thalassemia 2015-09-03 no assertion criteria provided clinical testing
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000984182 SCV001244507 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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