VCV000036331.29 - ClinVar

NM_000518.5(HBB):c.*96T>C

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(8)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(2); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000518.5(HBB):c.*96T>C

Variation ID: 36331 Accession: VCV000036331.29

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.4 11: 5225502 (GRCh38) [ NCBI UCSC ] 11: 5246732 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Oct 8, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000518.5:c.*96T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NC_000011.10:g.5225502A>G
NC_000011.9:g.5246732A>G
NG_000007.3:g.72114T>C
NG_046672.1:g.3437A>G
NG_053049.1:g.1823A>G
NG_059281.1:g.6570T>C
LRG_1232:g.6570T>C
LRG_1232t1:c.*96T>C

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:5225501:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00020

Trans-Omics for Precision Medicine (TOPMed) 0.00233

The Genome Aggregation Database (gnomAD) 0.00283

1000 Genomes Project 30x 0.00016

Links

ClinGen: CA342875 dbSNP: rs34029390 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
HBB		-	-	GRCh38 GRCh37	22	1835
LOC107133510	-	-	-	GRCh38	-	1785
LOC110006319	-	-	-	GRCh38	-	984

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
beta Thalassemia	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	May 28, 2019	RCV000029999.16
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000755281.28
HBB-related disorder	Likely benign (1)	no assertion criteria provided	Feb 28, 2020	RCV004541025.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
likely benign (Aug 18, 2011)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Beta Thalassemia (autosomal unknown) Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000052654.2 First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022	Publications: PubMed (6) PubMed: 1740317‚ 1536956‚ 20704537‚ 18603555‚ 1515649‚ 8270260 Comment: Converted during submission to Likely benign. Observation 1: Tissue: Blood Observation 2: Tissue: Blood Observation 3: Tissue: Blood Observation 4: Tissue: Blood Observation 5: Tissue: Blood Observation 6: Tissue: Blood
Likely benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001001217.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Likely benign (Apr 04, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV002504157.2 First in ClinVar: Apr 30, 2022 Last updated: Mar 04, 2023	Comment: See Variant Classification Assertion Criteria.
Likely benign (Jun 10, 2022)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000889355.4 First in ClinVar: Feb 18, 2019 Last updated: Jan 06, 2024	Publications: PubMed (13) PubMed: 24744638‚ 18096416‚ 18603555‚ 8270260‚ 1536956‚ 26418075‚ 30205726‚ 1740317‚ 1515649‚ 34362515‚ 22734587‚ 25572186‚ 27351925
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Beta-thalassemia HBB/LCRB Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001138213.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Uncertain significance (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Beta-thalassemia HBB/LCRB Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001262805.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Publications: PubMed (3) PubMed: 1515649‚ 1536956‚ 8270260 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) 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, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
Benign (Nov 24, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000603888.7 First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024
Likely benign (Feb 28, 2020)	no assertion criteria provided Method: clinical testing	HBB-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004784383.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

Germline Functional Evidence

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
[Genetic Effect Analysis of β-globin Gene 3'UTR+101G>C (HBB:c. *233G>C) Variant].	DU L	Zhongguo shi yan xue ye xue za zhi	2021	PMID: 34362515
Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T) (HBB: c.118C>T) and the Presence of ααα(anti-3.7)/αα in Greece. A Case Presentation.	Theodoridou S	Hemoglobin	2018	PMID: 30205726
Development of a High-Resolution Melting Approach for Scanning Beta Globin Gene Point Mutations in the Greek and Other Mediterranean Populations.	Chassanidis C	PloS one	2016	PMID: 27351925
Co-heredity of silent CAP + 1570 T>C (HBB:c*96T>C) defect and severe β-thal mutation: a cause of mild β-thalassemia intermedia.	Vinciguerra M	International journal of laboratory hematology	2016	PMID: 26418075
Identification of a novel mutation in the β-globin gene 3' untranslated region (HBB: c.*+118A > G) in Spain.	Herrera MA	Hemoglobin	2015	PMID: 25572186
Did the proband have thalassemia intermedia or severe thalassemia trait?	Ozsoylu S	Turkish journal of haematology : official journal of Turkish Society of Haematology	2012	PMID: 24744638
The +1,506 (A>C) mutation in the 3' untranslated region affects β-globin expression.	Hino M	Hemoglobin	2012	PMID: 22734587
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
Significance of borderline hemoglobin A2 values in an Italian population with a high prevalence of beta-thalassemia.	Giambona A	Haematologica	2008	PMID: 18603555
The molecular heterogeneity of beta-thalassemia in Greece.	Boussiou M	Blood cells, molecules & diseases	2008	PMID: 18096416
The T-->C mutation at position +96 of the untranslated region 3' to the terminating codon of the beta-globin gene is a rare polymorphism that does not cause a beta-thalassemia as previously ascribed.	Divoky V	Human genetics	1994	PMID: 8270260
Molecular characterization of beta-thalassemia in Czechoslovakia.	Indrak K	Human genetics	1992	PMID: 1740317
Two novel beta-thalassemia mutations in the 5' and 3' noncoding regions of the beta-globin gene.	Cai SP	Blood	1992	PMID: 1536956
The T----C substitution at nucleotide + 1570 of the beta-globin gene is a polymorphism.	Eng B	Blood	1992	PMID: 1515649
click to load more click to collapse

Text-mined citations for rs34029390 ...

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 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000518.5(HBB):c.*96T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34029390 ...