ClinVar Miner

Submissions for variant NM_000558.5(HBA1):c.96-1G>A

gnomAD frequency: 0.00017  dbSNP: rs34883113
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985716 SCV001134189 likely pathogenic not provided 2020-09-30 criteria provided, single submitter clinical testing The c.96-1G>A variant (also known as IVS-I-117G>A) is located in a canonical splice-acceptor site and is predicted to interfere with normal HBA1 mRNA splicing. This variant has been described to be of Asian Indian ancestry, and associated with alpha2 thalassemia and hemolytic anemia (HbVar (http://globin.cse.psu.edu/cgi-bin/hbvar/counter) and ITHANET (http://www.ithanet.eu/)). This variant has been reported as homozygous which was also compound heterozygous for Hb S and a beta+-thal, and as heterozygous with just Hb S alone or together with either -3.7kb deletion or -4.2 kb deletion in multiple affected individuals (PMID: 8251382 (1993)).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000985716 SCV001474361 pathogenic not provided 2020-08-03 criteria provided, single submitter clinical testing The HBA1 c.96-1G>A variant (rs34883113), also known as alpha1 IVS-I-117 (G->A), has been reported in multiple individuals affected with alpha thalassemia minor, found in-trans with either an alpha globin deletion or homozygously (Curuk 1993, HbVar database). This variant is found in the South Asian population with an overall allele frequency of 0.10% (21/21318 alleles) in the Genome Aggregation Database. This variant abolishes the canonical splice acceptor site of intron 1, which is likely to disrupt gene function. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar for alpha1 IVS-I-117 (G->A): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=1067 Curuk M et al. An IVS-I-117 (G-->A) acceptor splice site mutation in the alpha 1-globin gene is a nondeletional alpha-thalassaemia-2 determinant in an Indian population. Br J Haematol. 1993; 85(1):148-52.
Genetics and Molecular Pathology, SA Pathology RCV002466598 SCV002761437 pathogenic alpha Thalassemia 2020-03-20 criteria provided, single submitter clinical testing PVS1, PS3, PP5
Fulgent Genetics, Fulgent Genetics RCV002503142 SCV002816765 pathogenic Heinz body anemia; alpha Thalassemia; Hemoglobin H disease; Methemoglobinemia, alpha type; Erythrocytosis, familial, 7 2021-07-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003918611 SCV004732505 pathogenic HBA1-related condition 2023-11-16 criteria provided, single submitter clinical testing The HBA1 c.96-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant (also referred to as IVS-I-117) has been reported as a founder variant in the Indian population and is causative for alpha thalassemia (Curuk. 1993. PubMed ID: 8251382; Scheps. 2012. PubMed ID: 22738642). This variant is also interpreted as likely pathogenic and pathogenic in ClinVar. This variant is interpreted as pathogenic.

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