NM_000518.5(HBB):c.93-3T>G AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 24, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002477023.9

Allele description [Variation Report for NM_000518.5(HBB):c.93-3T>G]

NM_000518.5(HBB):c.93-3T>G

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.93-3T>G

Other names:

IVS I-128 (T>G); IVS1-128T>G

HGVS:

NC_000011.10:g.5226802A>C
NG_000007.3:g.70814T>G
NG_042296.1:g.333A>C
NG_046672.1:g.4737A>C
NG_059281.1:c.93-3T>G
NG_059281.1:g.5270T>G
NM_000518.5:c.93-3T>GMANE SELECT
LRG_1232t1:c.93-3T>G
LRG_1232:g.5270T>G
NC_000011.9:g.5248032A>C
NG_059281.1:c.93-3T>G
NM_000518.4:c.93-3T>G

Nucleotide change:

IVS1, T-G, -3

Links:

OMIM: 141900.0362; dbSNP: rs34527846

NCBI 1000 Genomes Browser:

rs34527846

Molecular consequence:

NM_000518.5:c.93-3T>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

DEAD-box helicase Dbp80 [Aedes albopictus]
DEAD-box helicase Dbp80 [Aedes albopictus]
gi|1702763817|ref|XP_019527968.2|

Protein
LOC100565422 [Anolis carolinensis]
LOC100565422 [Anolis carolinensis]
Gene ID:100565422

Gene

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
SCV002774341	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Aug 20, 2021)	unknown	clinical testing	PubMed (16) [See all records that cite these PMIDs] 22089620, 18759082, 25677748, 23915319, 26594346, 23094636, 2920213, 8435318, 8199027, 24719849, 20704537, 21119755, 19254853, 12368169, 9450794, 26467025
SCV004563859	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Likely pathogenic (Jan 24, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002774341

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Aug 20, 2021)

unknown

clinical testing

PubMed (16)
[See all records that cite these PMIDs]

SCV004563859

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Likely pathogenic
(Jan 24, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

See all PubMed Citations (16)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002774341.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

The variant found in at least one symptomatic individual. The variant is predicted to negatively affect a known splice site. The variant occurs in multiple cases with a lone recessive pathogenic/likely pathogenic variant in the same gene, and several have a phenotype known to be consistent with disease.

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004563859.1

#	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.93-3T>G variant (also known as IVS-I-128 (T->G), rs34527846, HbVar ID: 829) is reported in the compound heterozygous state in individuals with beta (+) thalassemia (Chiou 1993, Hussain 2017, Wong 1989, see link to HbVar and references therein). This variant is also reported in ClinVar (Variation ID: 36341), and is only observed on four alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical acceptor splice site. Based on available information, this variant is considered to be likely pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Chiou SS et al. Molecular basis and haematological characterization of beta-thalassaemia major in Taiwan, with a mutation of IVS-1 3' end TAG-->GAG in a Chinese patient. Br J Haematol. 1993 Jan;83(1):112-7. PMID: 8435318. Hussain A et al. Rare beta-Globin Gene Mutations in Pakistan. Hemoglobin. 2017 Mar;41(2):100-103. PMID: 28670940. Wong C et al. Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene. Blood. 1989 Mar;73(4):914-8. PMID: 2920213.

#	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

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine