NM_000518.5(HBB):c.*110T>C AND beta Thalassemia

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 5, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000445649.15

Allele description [Variation Report for NM_000518.5(HBB):c.*110T>C]

NM_000518.5(HBB):c.*110T>C

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.*110T>C

Other names:

AACAAA

HGVS:

NC_000011.10:g.5225488A>G
NG_000007.3:g.72128T>C
NG_046672.1:g.3423A>G
NG_053049.1:g.1809A>G
NG_059281.1:g.6584T>C
NM_000518.4(HBB):c.*110T>C
NM_000518.5:c.*110T>CMANE SELECT
LRG_1232t1:c.*110T>C
LRG_1232:g.6584T>C
NC_000011.9:g.5246718A>G
NM_000518.4(HBB):c.*110T>C
NM_000518.4:c.*110T>C
NM_000518.5:c.*110T>C

Nucleotide change:

3-UNT, T-C, +3

Links:

Genetic Testing Registry (GTR): GTR000500319; OMIM: 141900.0382; dbSNP: rs33978907

NCBI 1000 Genomes Browser:

rs33978907

Molecular consequence:

NM_000518.5:c.*110T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000537300	GeneReviews	no classification provided	not provided	germline	literature only
SCV001132413	Counsyl	no assertion criteria provided	Pathogenic (Nov 16, 2015)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 4018033, 22690826, 18294253
SCV001338948	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 4018033, 21119755, 22690826 Citation Link,
SCV002089181	Natera, Inc.	no assertion criteria provided	Pathogenic (Oct 6, 2020)	germline	clinical testing

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, literature only

Citations

PubMed

Analysis of beta globin mutations in the Indian population: presence of rare and novel mutations and region-wise heterogeneity.

Edison ES, Shaji RV, Devi SG, Moses A, Viswabandhya A, Mathews V, George B, Srivastava A, Chandy M.

Clin Genet. 2008 Apr;73(4):331-7. doi: 10.1111/j.1399-0004.2008.00973.x. Epub 2008 Feb 20.

PubMed [citation]

PMID:: 18294253

Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene.

Orkin SH, Cheng TC, Antonarakis SE, Kazazian HH Jr.

EMBO J. 1985 Feb;4(2):453-6.

PubMed [citation]

PMID:: 4018033
PMCID:: PMC554207

See all PubMed Citations (4)

Details of each submission

From GeneReviews, SCV000537300.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

#	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 Counsyl, SCV001132413.1

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001338948.1

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

Description

Variant summary: HBB c.*110T>C is located in the 3UTR downstream of the termination codon involves the alteration of a conserved nucleotide. The variant of interest is located within the known "polyA' tail, thus expected to alter mRNA expression, which is supported by Orkin_1985 functional findings. The variant allele was found at a frequency of 6.4e-05 in 31396 control chromosomes (gnomAD), which does not exceed the estimated maximal expected allele frequency of a pathogenic HBB variant (0.011). c.*110T>C has been reported in the literature in multiple individuals affected with Beta Thalassemia and implicated to be the third most common allele in India (Orkin_1985, Sinha_2009, Italia_2012). These data indicate that the variant is very likely to be associated with disease. Five ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (4x) and likely pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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 Natera, Inc., SCV002089181.1

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

#	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 26, 2024

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