NM_000518.5(HBB):c.*74A>G AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 16, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001812924.15

Allele description [Variation Report for NM_000518.5(HBB):c.*74A>G]

NM_000518.5(HBB):c.*74A>G

Genes:

LOC110006319:beta-globin gene 3' regulatory 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.*74A>G

HGVS:

NC_000011.10:g.5225524T>C
NG_000007.3:g.72092A>G
NG_046672.1:g.3459T>C
NG_053049.1:g.1845T>C
NG_059281.1:g.6548A>G
NM_000518.5:c.*74A>GMANE SELECT
LRG_1232t1:c.*74A>G
LRG_1232:g.6548A>G
NC_000011.9:g.5246754T>C
NM_000518.4:c.*74A>G

Links:

dbSNP: rs369101035

NCBI 1000 Genomes Browser:

rs369101035

Molecular consequence:

NM_000518.5:c.*74A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001472463	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Nov 25, 2019)	germline	clinical testing	Citation Link,
SCV004219846	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Sep 16, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24754789, 20437613, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001472463

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Nov 25, 2019)

germline

clinical testing

Citation Link,

SCV004219846

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Sep 16, 2022)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Evaluation of the validity of Hb A2 and mean corpuscular haemoglobin action values in antenatal screening for beta thalassaemia carriers in England.

Daniel Y, Cartwright R, Rennie K, Streetly A, Howard J.

Br J Haematol. 2014 Aug;166(4):607-11. doi: 10.1111/bjh.12917. Epub 2014 Apr 23.

PubMed [citation]

PMID:: 24754789

Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE).

Al-Gazali L, Ali BR.

Hum Mutat. 2010 May;31(5):505-20. doi: 10.1002/humu.21232. Review.

PubMed [citation]

PMID:: 20437613

See all PubMed Citations (3)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001472463.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The HBB c.*74A>G variant (rs369101035) is reported in the literature in individuals affected with beta-thalassemia or mild anemia, although its clinical significance was not determined in these studies (Al-Gazali 2010, Daniel 2014). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant occurs in the 3' untranslated region at a nucleotide that is moderately conserved and is located upstream of the poly(A) signal. However, given the lack of clinical and functional data, the significance of the c.*74A>G variant is uncertain at this time. References: Al-Gazali L and Ali BR. Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE). Hum Mutat. 2010 May;31(5):505-20. Daniel Y et al. Evaluation of the validity of Hb A2 and mean corpuscular haemoglobin action values in antenatal screening for beta thalassaemia carriers in England. Br J Haematol. 2014 Aug;166(4):607-11.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219846.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 29, 2024

ClinVar

Relating variation to medicine