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NM_000558.5(HBA1):c.96-1G>A AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Sep 30, 2020
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000985716.15

Allele description [Variation Report for NM_000558.5(HBA1):c.96-1G>A]

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

Genes:
LOC106804613:hemoglobin subunit alpha 1 recombination region [Gene]
HBA1:hemoglobin subunit alpha 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000558.5(HBA1):c.96-1G>A
HGVS:
  • NC_000016.10:g.176928G>A
  • NG_000006.1:g.37791G>A
  • NG_046166.1:g.2411G>A
  • NG_059186.1:g.5278G>A
  • NM_000558.5:c.96-1G>AMANE SELECT
  • LRG_1225t1:c.96-1G>A
  • LRG_1225:g.5278G>A
  • NC_000016.9:g.226927G>A
  • NM_000558.3:c.96-1G>A
  • NM_000558.4:c.96-1G>A
Links:
dbSNP: rs34883113
NCBI 1000 Genomes Browser:
rs34883113
Molecular consequence:
  • NM_000558.5:c.96-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001134189Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)		Likely pathogenic
(Sep 30, 2020) 		unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001474361ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Pathogenic
(Aug 3, 2020) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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.

Cürük MA, Baysal E, Gupta RB, Sharma S, Huisman TH.

Br J Haematol. 1993 Sep;85(1):148-52.

PubMed [citation]
PMID:
8251382

Identification of a new HBA1 gene mutation (HBA1:c.301-2A>T) in cis with Hb Riccarton (HBA1:c.154G>A) [α51(CE9)Gly→Ser].

Scheps KG, Binaghi A, Varela V.

Hemoglobin. 2012;36(5):504-7.

PubMed [citation]
PMID:
22738642
See all PubMed Citations (5)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134189.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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)).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001474361.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024