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

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(2);Likely benign(2);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: May 19, 2021)
Last evaluated:
Apr 23, 2021
Accession:
VCV000036291.11
Variation ID:
36291
Description:
single nucleotide variant
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NM_000518.5(HBB):c.-31C>T

Allele ID
44955
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
11p15.4
Genomic location
11: 5227052 (GRCh38) GRCh38 UCSC
11: 5248282 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_1232:g.5020C>T
LRG_1232t1:c.-31C>T
NC_000011.10:g.5227052G>A
... more HGVS
Protein change
-
Other names
CAP +20 C>T
Canonical SPDI
NC_000011.10:5227051:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Links
ClinGen: CA342844
dbSNP: rs63750628
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, single submitter Dec 5, 2018 RCV000029956.5
Likely benign 1 criteria provided, single submitter Jul 16, 2020 RCV000507019.4
Uncertain significance 1 criteria provided, single submitter Sep 11, 2018 RCV000755548.3
Benign 1 criteria provided, single submitter Apr 27, 2017 RCV001104361.1
Benign 1 criteria provided, single submitter Apr 27, 2017 RCV001104363.1
Uncertain significance 1 criteria provided, single submitter Apr 27, 2017 RCV001104362.1
Likely benign 1 criteria provided, single submitter Apr 23, 2021 RCV001420720.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
HBB - - GRCh38
GRCh37
45 1293
LOC106099062 - - - GRCh38 - 702
LOC107133510 - - - GRCh38 - 1226

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Jul 16, 2020)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603911.4
Submitted: (Dec 11, 2020)
Evidence details
Likely benign
(Apr 23, 2021)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052611.2
Submitted: (May 19, 2021)
Evidence details
Publications
PubMed (11)
Comment:
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 … (more)
Uncertain significance
(Dec 05, 2018)
criteria provided, single submitter
Method: clinical testing
beta Thalassemia
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000914521.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The HBB c.-31C>T variant, commonly referred to as 5’UTR+20, C>T, has been described in at least four studies in which it is found in cis … (more)
Uncertain significance
(Sep 11, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888153.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (8)
Benign
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Hb SS disease
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001261218.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Uncertain significance
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Fetal hemoglobin quantitative trait locus 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001261220.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Benign
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Hemoglobin E
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001261221.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Benign
(Nov 25, 2019)
no assertion criteria provided
Method: curation
beta Thalassemia
Allele origin: germline
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics
Accession: SCV001244457.1
Submitted: (Nov 25, 2019)
Evidence details
Publications
PubMed (1)
Other databases
https://ithanet.eu/db/ithagenes?…

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Interaction of an α-Globin Gene Triplication with β-Globin Gene Mutations in Iranian Patients with β-Thalassemia Intermedia. Farashi S Hemoglobin 2015 PMID: 26084319
The spectrum of β-thalassemia mutations in Hatay, Turkey: reporting three new mutations. Aldemir O Hemoglobin 2014 PMID: 25155404
Frequency of beta-thalassemia or beta-hemoglobinopathy carriers simultaneously affected with alpha-thalassemia in Iran. Alizadeh S Clinical laboratory 2014 PMID: 25016698
Identification of three new nucleotide substitutions in the β-globin gene: laboratoristic approach and impact on genetic counselling for beta-thalassaemia. Vinciguerra M European journal of haematology 2014 PMID: 24401016
Association in cis of the mutations +20 (C>T) in the 5' untranslated region and IVS-II-745 (C>G) on the β-globin gene. Ropero P Hemoglobin 2013 PMID: 23425204
The spectrum of β-thalassemia mutations in Gaza Strip, Palestine. Sirdah MM Blood cells, molecules & diseases 2013 PMID: 23321370
High prevalence of rare mutations in the Beta globin gene in an ethnic group in iran. Galehdari H Iranian Red Crescent medical journal 2011 PMID: 22737496
Comprehensive spectrum of the β-Thalassemia mutations in Khuzestan, southwest Iran. Galehdari H Hemoglobin 2010 PMID: 20854120
ThalassoChip, an array mutation and single nucleotide polymorphism detection tool for the diagnosis of β-thalassaemia. Shammas C Clinical chemistry and laboratory medicine 2010 PMID: 20704537
Hemoglobinopathies in North Africa: a review. Haj Khelil A Hemoglobin 2010 PMID: 20113284
Acute splenic infarct in beta-thalassemia minor: a novel combination of heterozygous beta-globin mutations with latent phenotypes and the clinical implications. Liaw DC Hemoglobin 2009 PMID: 19657842
Molecular basis of beta-thalassemia in Morocco: possible origins of the molecular heterogeneity. Agouti I Genetic testing 2008 PMID: 18976160
Real-time PCR for single-cell genotyping in sickle cell and thalassemia syndromes as a rapid, accurate, reliable, and widely applicable protocol for preimplantation genetic diagnosis. Vrettou C Human mutation 2004 PMID: 15108284
Spectrum of beta thalassemia mutations and HbF levels in the heterozygous Moroccan population. Lemsaddek W American journal of hematology 2003 PMID: 12827652
Validation of a recombinant DNA construct (micro LCR and full-length beta-globin gene) for quantification of human beta-globin expression: application to mutations in the promoter, intronic, and 5'- and 3'-untranslated regions of the human beta-globin gene. Irenge LM Clinical chemistry 2002 PMID: 12324499
Molecular spectrum of beta-thalassemia in the Iranian Province of Hormozgan. Yavarian M Hemoglobin 2001 PMID: 11300348
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 Blood 1989 PMID: 2713503
https://ithanet.eu/db/ithagenes?ithaID=37 - - - -

Text-mined citations for rs63750628...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021