NM_000518.4(HBB):c.19G>A (p.Glu7Lys) AND Sickle cell-hemoglobin C disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 14, 2022
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:: RCV003150807.8

Allele description [Variation Report for NM_000518.4(HBB):c.19G>A (p.Glu7Lys)]

NM_000518.4(HBB):c.19G>A (p.Glu7Lys)

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_000518.4(HBB):c.19G>A (p.Glu7Lys)

Other names:

E6K; HbC

HGVS:

NC_000011.10:g.5227003C>T
NG_000007.3:g.70613G>A
NG_042296.1:g.534C>T
NG_046672.1:g.4938C>T
NG_059281.1:g.5069G>A
NM_000518.5:c.19G>AMANE SELECT
NP_000509.1:p.Glu7Lys
NP_000509.1:p.Glu7Lys
LRG_1232t1:c.19G>A
LRG_1232:g.5069G>A
LRG_1232p1:p.Glu7Lys
NC_000011.9:g.5248233C>T
NM_000518.4:c.19G>A
P68871:p.Glu7Lys

Protein change:

E7K; Glu6Lys

Links:

Genetic Testing Registry (GTR): GTR000500319; HBVAR: 227; UniProtKB: P68871#VAR_002864; OMIM: 141900.0010; OMIM: 141900.0038; dbSNP: rs33930165

NCBI 1000 Genomes Browser:

rs33930165

Molecular consequence:

NM_000518.5:c.19G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Sickle cell-hemoglobin C disease
Synonyms:: Hemoglobin SC disease; Sickle cell-hemoglobin C disease syndrome; Hemoglobin S/C
Identifiers:: MONDO: MONDO:0016669; MeSH: D006450; MedGen: C0019034; Orphanet: 251365

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
SCV003839040	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 14, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23297836, 23591685, 2888754, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003839040

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 14, 2022)

germline

clinical testing

PubMed (4)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The clinical and laboratory spectrum of Hb C [β6(A3)Glu→Lys, GAG>AAG] disease.

Cook CM, Smeltzer MP, Mortier NA, Kirk SE, Despotovic JM, Ware RE, Hankins JS.

Hemoglobin. 2013;37(1):16-25. doi: 10.3109/03630269.2012.753547.

PubMed [citation]

PMID:: 23297836

The distribution of haemoglobin C and its prevalence in newborns in Africa.

Piel FB, Howes RE, Patil AP, Nyangiri OA, Gething PW, Bhatt S, Williams TN, Weatherall DJ, Hay SI.

Sci Rep. 2013;3:1671. doi: 10.1038/srep01671.

PubMed [citation]

PMID:: 23591685
PMCID:: PMC3628164

See all PubMed Citations (4)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV003839040.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This HBB variant (rs33930165) reaches polymorphic frequency (>1%) within the African/African American subpopulation in a large population dataset (gnomAD: 335/24966 total alleles, 1.342%, 1 homozygote) and has been reported in ClinVar. Also known as p.Glu6Lys and HbC, it has been reported in a homozygous or compound heterozygous state in individuals with beta-hemoglobinopathies. Heterozygosity for p.Glu7Lys in the absence of another pathogenic HBB variant results in Hemoglobin C trait (HbAC), which is clinically silent. Two bioinformatic tools queried predict that this substitution would tolerated, but experimental studies have shown that this variant affects the physical and kinetic properties of the hemoglobin protein. Bioinformatic analysis predicts that this missense variant would not affect normal exon 1 splicing, although this has not been confirmed experimentally to our knowledge. We consider c.19G>A (p.Glu7Lys) to be 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

Last Updated: May 19, 2024

ClinVar

Relating variation to medicine