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NM_000518.5(HBB):c.112del (p.Trp38fs) AND beta Thalassemia

Germline classification:
Pathogenic (5 submissions)
Last evaluated:
Feb 2, 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:
RCV001078307.18

Allele description [Variation Report for NM_000518.5(HBB):c.112del (p.Trp38fs)]

NM_000518.5(HBB):c.112del (p.Trp38fs)

Genes:
LOC106099062:HBB recombination region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]
Variant type:
Deletion
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000518.5(HBB):c.112del (p.Trp38fs)
Other names:
CD 36/37 (-T)
HGVS:
  • NC_000011.10:g.5226781del
  • NC_000011.9:g.5248010del
  • NG_000007.3:g.70836del
  • NG_042296.1:g.312del
  • NG_046672.1:g.4716del
  • NG_059281.1:g.5292del
  • NM_000518.5:c.112delMANE SELECT
  • NP_000509.1:p.Trp38fs
  • LRG_1232t1:c.112del
  • HBB:c.112delT
  • LRG_1232:g.5292del
  • LRG_1232p1:p.Trp38fs
  • NC_000011.10:g.5226780delA
  • NC_000011.9:g.5248010del
  • NC_000011.9:g.5248011del
  • NC_000011.9:g.5248011delA
  • NM_000518.4:c.112delT
  • NM_000518.5:c.112delTMANE SELECT
  • p.Trp38Glyfs*24
Protein change:
W38fs
Links:
Genetic Testing Registry (GTR): GTR000500319; HBVAR: 840; OMIM: 141900.0331; OMIM: 141900.0341; dbSNP: rs63750532
NCBI 1000 Genomes Browser:
rs63750532
Molecular consequence:
  • NM_000518.5:c.112del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
beta Thalassemia (BTHAL)
Synonyms:
Cooley's anemia; Erythroblastic anemia; Mediterranean anemia
Identifiers:
MONDO: MONDO:0019402; MedGen: C0005283; Orphanet: 848

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001244471The ITHANET community portal, The Cyprus Institute of Neurology and Genetics
no assertion criteria provided
Pathogenic
(Nov 25, 2019)
germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001251903Genomic Research Center, Shahid Beheshti University of Medical Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(May 3, 2020)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001810471Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jul 22, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002089229Natera, Inc.
no assertion criteria provided
Pathogenic
(Mar 17, 2017)
germlineclinical testing

SCV004848885Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Feb 2, 2023)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular analyses of beta-thalassemia in Iran.

Nozari G, Rahbar S, Golshaiyzan A, Rahmanzadeh S.

Hemoglobin. 1995;19(6):425-31. No abstract available.

PubMed [citation]
PMID:
8718703

The Frequency of HBB Mutations Among β-Thalassemia Patients in Hamadan Province, Iran.

Jalilian M, Azizi Jalilian F, Ahmadi L, Amini R, Esfehani H, Sosanian M, Rabbani B, Maleki M, Mahdieh N.

Hemoglobin. 2017 Jan;41(1):61-64. doi: 10.1080/03630269.2017.1302468. Epub 2017 Apr 10.

PubMed [citation]
PMID:
28391758
See all PubMed Citations (10)

Details of each submission

From The ITHANET community portal, The Cyprus Institute of Neurology and Genetics, SCV001244471.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV001251903.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV001810471.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV002089229.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848885.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

The p.Trp38GlyfsX24 (c.112delT or "36/37(-T)") variant in HBB has been reported in over 30 individuals with beta thalassemia (Yılmaz 2019 PMID: 31411089, Yavarian 2001 PMID: 11300348, Tekes 2022, Rund 1991 PMID: 1986379, Moradi 2020 PMID: 32869674, Kiani 2007 PMID: 17654071, Jalilian 2017 PMID: 28391758, Guzelgul 2020 PMID: 32664780, Amin 2020 PMID: 33335418). It was absent from large population studies. This variant has also been reported in ClinVar (Variation ID 15431). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 38 and leads to a premature termination codon 24 amino acids downstream. This is predicted to lead to a truncated or absent protein. Loss of function of the HBB gene is an established disease mechanism in autosomal recessive beta thalassemia. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive beta thalassemia. ACMG/AMP Criteria applied: PVS1, PS4, PM2_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024