NM_000518.5(HBB):c.-31C>T AND not specified

Clinical significance:Likely benign (Last evaluated: Apr 23, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001420720.1

Allele description [Variation Report for NM_000518.5(HBB):c.-31C>T]

NM_000518.5(HBB):c.-31C>T

Genes:
LOC106099062:HBB recombination region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000518.5(HBB):c.-31C>T
Other names:
CAP +20 C>T
HGVS:
  • NC_000011.10:g.5227052G>A
  • NG_000007.3:g.70564C>T
  • NG_042296.1:g.583G>A
  • NG_046672.1:g.4987G>A
  • NG_059281.1:g.5020C>T
  • NM_000518.5:c.-31C>TMANE SELECT
  • LRG_1232t1:c.-31C>T
  • LRG_1232:g.5020C>T
  • NC_000011.9:g.5248282G>A
  • NM_000518.4:c.-31C>T
Links:
dbSNP: rs63750628
NCBI 1000 Genomes Browser:
rs63750628
Molecular consequence:
  • NM_000518.5:c.-31C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000052611Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Apr 23, 2021)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

A C----T substitution at nt--101 in a conserved DNA sequence of the promotor region of the beta-globin gene is associated with "silent" beta-thalassemia.

Gonzalez-Redondo JM, Stoming TA, Kutlar A, Kutlar F, Lanclos KD, Howard EF, Fei YJ, Aksoy M, Altay C, Gurgey A, et al.

Blood. 1989 May 1;73(6):1705-11.

PubMed [citation]
PMID:
2713503

ThalassoChip, an array mutation and single nucleotide polymorphism detection tool for the diagnosis of β-thalassaemia.

Shammas C, Papasavva T, Felekis X, Christophorou C, Roomere H, Synodinos JT, Kanavakis E, El-Khateeb M, Hamamy H, Mahmoud T, Shboul M, El Beshlawy A, Filon D, Hussein IR, Galanello R, Romeo G, Kleanthous M.

Clin Chem Lab Med. 2010 Dec;48(12):1713-8. doi: 10.1515/CCLM.2010.331. Epub 2010 Aug 13.

PubMed [citation]
PMID:
20704537
See all PubMed Citations (11)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052611.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

Variant summary: HBB c.-31C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 6.4e-05 in 250664 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in HBB causing Beta Thalassemia (6.4e-05 vs 0.011), allowing no conclusion about variant significance. c.-31C>T has been widely reported in the literature to co-occur in cis with other disease causing variants such as IVS-II-745C>G (c.316-106C>G) in individuals affected with Beta Thalassemia (example, Gonzalez-Redondo_1989, Lemsaddek_2003, Yavarian_2001, Galehdari_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Beta Thalassemia. Locus specific databases report this variant predominantly as benign. At least one publication reports experimental evidence evaluating an impact on expression of beta globin mRNA, however, does not allow convincing conclusions about the variant effect (example, Irenge_2002). Five clinical diagnostic laboratories and a database (ITHANET) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple submitters reported the variant with conflicting assessments (benign, n=2; likely benign; n=1, VUS, n=3). One submitter reports both a benign and VUS classifications. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Nov 27, 2021

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