VCV000226625.15 - ClinVar

NM_001122659.3(EDNRB):c.552T>C (p.Ser184=)

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.

(6)

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.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001122659.3(EDNRB):c.552T>C (p.Ser184=)

Variation ID: 226625 Accession: VCV000226625.15

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q22.3 13: 77903539 (GRCh38) [ NCBI UCSC ] 13: 78477674 (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	May 29, 2016	Sep 29, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001122659.3:c.552T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001116131.1:p.Ser184=	synonymous
NM_000115.5:c.552T>C	NP_000106.1:p.Ser184=	synonymous
NM_001201397.2:c.822T>C	NP_001188326.1:p.Ser274=	synonymous
NM_003991.4:c.552T>C	NP_003982.1:p.Ser184=	synonymous
NC_000013.11:g.77903539A>G
NC_000013.10:g.78477674A>G
NG_011630.3:g.76185T>C

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000013.11:77903538: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.

0.01617 (A)

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

1000 Genomes Project 30x 0.98173

Trans-Omics for Precision Medicine (TOPMed) 0.98361

1000 Genomes Project 0.98383

The Genome Aggregation Database (gnomAD) 0.98435

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.98493

Exome Aggregation Consortium (ExAC) 0.99488

The Genome Aggregation Database (gnomAD), exomes 0.99566

Links

ClinGen: CA7012312 dbSNP: rs5348 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.
EDNRB		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	91	381
EDNRB-AS1	-	-	-	GRCh38	-	232

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.
not specified	Benign (1)	criteria provided, single submitter	Nov 24, 2014	RCV000220746.4
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV001522920.7
Waardenburg syndrome type 4A	Benign (1)	criteria provided, single submitter	Jul 30, 2021	RCV001658010.2
ABCD syndrome	Benign (1)	criteria provided, single submitter	Jul 30, 2021	RCV001658011.2
ABCD syndrome Hirschsprung disease, susceptibility to, 2 Waardenburg syndrome type 4A	Benign (1)	criteria provided, single submitter	Oct 25, 2021	RCV002503839.1

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.
Benign (Nov 24, 2014)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000269071.2 First in ClinVar: May 29, 2016 Last updated: May 29, 2016	Comment: Ser274Ser in exon 3 of EDNRB: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue … (more) Ser274Ser in exon 3 of EDNRB: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.4% (194/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs5348). (less) Number of individuals with the variant: 1048
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	ABCD syndrome Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001875932.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Benign (Jul 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Waardenburg syndrome type 4A Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001875934.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Sex: mixed
Benign (Oct 25, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Waardenburg syndrome type 4A Hirschsprung disease, susceptibility to, 2 ABCD syndrome Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002807974.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001732553.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005230956.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024

Comment:

Ser274Ser in exon 3 of EDNRB: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 4.4% (194/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs5348).

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.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs5348 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001122659.3(EDNRB):c.552T>C (p.Ser184=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs5348 ...