VCV000446746.3 - ClinVar

NM_000518.4(HBB):c.[34G>A;364G>A]

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.

(1)

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.

other

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000518.4(HBB):c.[34G>A;364G>A]

Other names: HBB, GLU121LYS, VAL11ILE
Hb O-Tibesti
Functional consequence: -
Links: ClinGen: CA037973; OMIM: 141900.0507

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
LOC106099062	-	-	-	GRCh38	-	863
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.
HEMOGLOBIN O (TIBESTI)	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016863.12

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.
other (Dec 12, 2017)	no assertion criteria provided Method: literature only	HEMOGLOBIN O (TIBESTI) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000037133.4 First in ClinVar: Apr 04, 2013 Last updated: Jul 24, 2016	Publications: PubMed (1) PubMed: 11939508 Comment on evidence: Prehu et al. (2002) described a heterozygous hemoglobin variant that combined the change of Hb O-Arab (141900.0202) and Hb Hamilton (141900.0099) on the same HBB … (more) Prehu et al. (2002) described a heterozygous hemoglobin variant that combined the change of Hb O-Arab (141900.0202) and Hb Hamilton (141900.0099) on the same HBB allele. The other allele carried the Hb S mutation (141900.0243). The patient was a child of Chad-Sudanese descent, suffering from a sickle cell syndrome. Compared to the classic description of the Hb S/Hb O-Arab association, the additional Hb Hamilton mutation did not seem to modify the clinical presentation. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Sickle Cell Disease.	Adam MP	-	2023	PMID: 20301551
Rare coding variation provides insight into the genetic architecture and phenotypic context of autism.	Fu JM	Nature genetics	2022	PMID: 35982160
Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes.	Zhou X	Nature genetics	2022	PMID: 35982159
Spectrum of HBB gene mutations among 696 β-thalassemia patients and carriers in Southern Vietnam.	Xinh PT	Molecular biology reports	2022	PMID: 35023007
[Effect of high-throughput sequencing for the prevention and control of thalassemia].	Chen Y	Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics	2020	PMID: 32472543
Curating the gnomAD database: Report of novel variants in the globin-coding genes and bioinformatics analysis.	Scheps KG	Human mutation	2020	PMID: 31553106
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain.	Scheps KG	European journal of haematology	2018	PMID: 29319890
Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies.	Shang X	EBioMedicine	2017	PMID: 28865746
Coinheritance of Hb D-Punjab and β-thalassemia: diagnosis and implications in prenatal diagnosis.	Das S	Hemoglobin	2015	PMID: 25666204
Molecular diagnostics of the HBB gene in an Omani cohort using bench-top DNA Ion Torrent PGM technology.	Hassan SM	Blood cells, molecules & diseases	2014	PMID: 24880717
The effect of hydroxyurea on compound heterozygotes for sickle cell-hemoglobin D-Punjab--a single centre experience in eastern India.	Patel S	Pediatric blood & cancer	2014	PMID: 24616059
Fetal hemoglobin and alpha thalassemia modulate the phenotypic expression of HbSD-Punjab.	Patel DK	International journal of laboratory hematology	2014	PMID: 24245819
Prevalence and genetic analysis of α-thalassemia and β-thalassemia in Chongqing area of China.	Yao XY	Gene	2013	PMID: 24055728
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.	Lazarin GA	Genetics in medicine : official journal of the American College of Medical Genetics	2013	PMID: 22975760
Bone marrow necrosis and sickle cell crisis associated with double heterozygosity for HbS and HbOARAB.	Rossi P	American journal of hematology	2011	PMID: 20954261
Compound heterozygosity of Hb Hamilton and de novo mutated HbM Saskatoon.	Brunner-Agten S	Annals of hematology	2010	PMID: 19727720
Impact of single nucleotide polymorphisms in HBB gene causing haemoglobinopathies: in silico analysis.	George Priya Doss C	New biotechnology	2009	PMID: 19429541
Hb O-Tibesti [beta121(GH4)Glu-->Lys; beta11(A8)Val-->Ile], a hemoglobin variant carrying in the same beta chain the substitutions of Hb O-Arab and Hb Hamilton, found in combination with Hb S [beta6(A3)Glu-->Val].	Préhu C	Hemoglobin	2002	PMID: 11939508
Hb O-Tibesti [beta121(GH4)Glu-->Lys; beta11(A8)Val-->Ile], a hemoglobin variant carrying in the same beta chain the substitutions of Hb O-Arab and Hb Hamilton, found in combination with Hb S [beta6(A3)Glu-->Val].	Préhu C	Hemoglobin	2002	PMID: 11939508
Characterization of syntenin, a syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments.	Zimmermann P	Molecular biology of the cell	2001	PMID: 11179419
The erythrocyte effects of haemoglobin O(ARAB).	Nagel RL	British journal of haematology	1999	PMID: 10583251
Hemoglobin S/O(Arab): thirteen new cases and review of the literature.	Zimmerman SA	American journal of hematology	1999	PMID: 10203101
HbS-oman heterozygote: a new dominant sickle syndrome.	Nagel RL	Blood	1998	PMID: 9834244
Hb O-Arab [beta 121(GH4)Glu-->Lys]: association with DNA polymorphisms of African ancestry in two Mediterranean families.	Lacerra G	Hemoglobin	1993	PMID: 7908281
Hemoglobin variants and activity of the (K+Cl-) cotransport system in human erythrocytes.	Olivieri O	Blood	1992	PMID: 1732017
Identification of Hb Hamilton or beta 11(A8)Val----Ile gene by the polymerase chain reaction amplification technique.	Manca L	Biochimica et biophysica acta	1992	PMID: 1610915
Hb H disease in association with the silent beta chain variant Hb Hamilton or alpha 2 beta 2(11)(A8)Val----Ile.	Su CW	Hemoglobin	1992	PMID: 1428944
Hemoglobin Hamilton [beta 11(A8)Val----Ile] in Sardinia.	Manca L	Hemoglobin	1987	PMID: 3623977
The interaction of hemoglobin O Arab with Hb S and beta+ thalassemia among Israeli Arabs.	Rachmilewitz EA	Human genetics	1985	PMID: 3859465
Hb Doha or alpha 2 beta 2[X-N-Met-1(NA1)Val----Glu]; a new beta-chain abnormal hemoglobin observed in a Qatari female.	Kamel K	Biochimica et biophysica acta	1985	PMID: 3840039
Hemoglobin Hamilton or alpha 2 beta 2 11(A8)Val leads to Ile: a silent beta-chain variant detected by Triton X-100 acid-urea polyacrylamide gel electrophoresis.	Wong SC	American journal of hematology	1984	PMID: 6695908
The detection and use of hemoglobin mutants in the direct analysis of human globin genes.	Little PF	Blood	1980	PMID: 6246994
Homozygous hemoglobin O Arab in a gypsy family in Yugoslavia.	Efremov GD	Hemoglobin	1977	PMID: 893136
Postsynthetic deamidation of hemoglobin Providence (beta 82 Lys replaced by Asn, Asp) and its effect on oxygen transport.	Charache S	The Journal of clinical investigation	1977	PMID: 14973
Twelve families with Hb O Arab in the Burgas district of Bulgaria. Observations on sixteen examples of Hb O Arab-beta (0) thalassaemia.	Kantchev KN	Humangenetik	1975	PMID: 1112610
Hemoglobin O arab in four negro families and its interaction with hemoglobin S and hemoglobin C.	Milner PF	The New England journal of medicine	1970	PMID: 5481775
High incidence of haemoglobin G Accra in a rural district in Jamaica.	Milner PF	Journal of medical genetics	1967	PMID: 5619995
"Hemoglobin alpha2beta2-121ys" chemical identification in an egyptian family.	Kamel KA	Science (New York, N.Y.)	1967	PMID: 5609824
Haemoglobin O Arab in Sudanese.	Vella F	Nature	1966	PMID: 5915974
Haemoglobin O in An Arab Family.	Ramot B	British medical journal	1960	PMID: 20788973
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Text-mined citations for this variant ...

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000518.4(HBB):c.[34G>A;364G>A]

Variant Details

NM_000518.4(HBB):c.[34G>A;364G>A]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...