VCV000015308.4 - ClinVar

NM_000518.4(HBB):c.98T>C (p.Leu33Pro)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000518.4(HBB):c.98T>C (p.Leu33Pro)

Variation ID: 15308 Accession: VCV000015308.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.4 11: 5226794 (GRCh38) [ NCBI UCSC ] 11: 5248024 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 25, 2018	Jan 6, 2024	Jan 20, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000518.5:c.98T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000509.1:p.Leu33Pro	missense
NC_000011.10:g.5226794A>G
NC_000011.9:g.5248024A>G
NG_000007.3:g.70822T>C
NG_042296.1:g.325A>G
NG_046672.1:g.4729A>G
NG_059281.1:g.5278T>C
LRG_1232:g.5278T>C
LRG_1232t1:c.98T>C	LRG_1232p1:p.Leu33Pro

... more HGVS ... less HGVS

Protein change

L33P

Other names

L32P
Hb Abraham Lincoln
Hb Kobe

Canonical SPDI

NC_000011.10:5226793:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

HBVAR: 293 ClinGen: CA125096 OMIM: 141900.0218 dbSNP: rs33948578 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
HBB		-	-	GRCh38 GRCh37	22	1835
LOC106099062	-	-	-	GRCh38	-	863
LOC107133510	-	-	-	GRCh38	-	1785

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
HEMOGLOBIN PERTH	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016546.12
HEMOGLOBIN ABRAHAM LINCOLN	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016547.12
HEMOGLOBIN KOBE	other (1)	no assertion criteria provided	Dec 12, 2017	RCV000016548.12
not provided	Pathogenic (1)	criteria provided, single submitter	Jan 20, 2023	RCV003480032.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 20, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV004224306.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Comment: PP3, PM2, PM6, PS4_moderate Number of individuals with the variant: 1
other (Dec 12, 2017)	no assertion criteria provided Method: literature only	HEMOGLOBIN KOBE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036816.4 First in ClinVar: Apr 04, 2013 Last updated: Mar 25, 2018	Publications: PubMed (4) PubMed: 4127713‚ 4352462‚ 6153383‚ 6998928 Comment on evidence: This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et … (more) This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et al. (1980). (less)
other (Dec 12, 2017)	no assertion criteria provided Method: literature only	HEMOGLOBIN PERTH Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036814.4 First in ClinVar: Apr 04, 2013 Last updated: Mar 25, 2018	Publications: PubMed (4) PubMed: 4127713‚ 4352462‚ 6153383‚ 6998928 Comment on evidence: This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et … (more) This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et al. (1980). (less)
other (Dec 12, 2017)	no assertion criteria provided Method: literature only	HEMOGLOBIN ABRAHAM LINCOLN Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036815.4 First in ClinVar: Apr 04, 2013 Last updated: Mar 25, 2018	Publications: PubMed (4) PubMed: 4127713‚ 4352462‚ 6153383‚ 6998928 Comment on evidence: This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et … (more) This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et al. (1980). (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Abnormal hemoglobins in Japan.	Shibata S	Hemoglobin	1980	PMID: 6998928
A severe hemolytic anemia related to a new case of hemoglobin Perth (Abraham Lincoln) in a French patient.	Rousseaux J	Hemoglobin	1980	PMID: 6153383
Hemoglobin Abraham Lincoln, beta32 (B14) leucine leads to proline. An unstable variant producing severe hemolytic disease.	Honig GR	The Journal of clinical investigation	1973	PMID: 4352462
Haemoglobin Perth: beta-32 (B14) Leu leads to Pro, an unstable haemoglobin causing haemolysis.	Jackson JM	British journal of haematology	1973	PMID: 4127713

Text-mined citations for rs33948578 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000518.4(HBB):c.98T>C (p.Leu33Pro)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs33948578 ...