p.Ile277Ile in exon 3 of EDNRB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 2.9% (128/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5349).
ClinVar Genomic variation as it relates to human health
NM_001122659.3(EDNRB):c.561C>T (p.Ile187=)
Germline
Classification
Help
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.
(8)
Help
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/Likely benign
8
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.561C>T (p.Ile187=)
Variation ID: 226626 Accession: VCV000226626.22
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q22.3 13: 77903530 (GRCh38) [ NCBI UCSC ] 13: 78477665 (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 Oct 2, 2016 Sep 29, 2024 Jan 26, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001122659.3:c.561C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001116131.1:p.Ile187= synonymous NM_000115.5:c.561C>T NP_000106.1:p.Ile187= synonymous NM_001201397.2:c.831C>T NP_001188326.1:p.Ile277= synonymous NM_003991.4:c.561C>T NP_003982.1:p.Ile187= synonymous NC_000013.11:g.77903530G>A NC_000013.10:g.78477665G>A NG_011630.3:g.76194C>T - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000013.11:77903529:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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.
-
0.01138 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00548
Exome Aggregation Consortium (ExAC) 0.00583
1000 Genomes Project 30x 0.01077
1000 Genomes Project 0.01138
The Genome Aggregation Database (gnomAD) 0.01149
Trans-Omics for Precision Medicine (TOPMed) 0.01211
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01322
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|---|---|---|---|---|
| Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 3, 2021 | RCV000213751.17 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 6, 2018 | RCV000289796.5 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 26, 2024 | RCV000969641.9 |
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
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000302324.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Jan 13, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000269072.2
First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018 |
Comment:
p.Ile277Ile in exon 3 of EDNRB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue … (more)
p.Ile277Ile in exon 3 of EDNRB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 2.9% (128/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5349). (less)
Number of individuals with the variant: 22
|
|
|
Likely benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hirschsprung disease, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000384817.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
|
|
Benign
(Mar 09, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000706484.2
First in ClinVar: Oct 02, 2016 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Benign
(Mar 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV001880183.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
|
|
|
Benign
(May 24, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000730642.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 17618893, 12628594, 22993632, 20009762)
|
|
|
Benign
(Jan 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001117168.5
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005217635.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
Comment:
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Comment:
This variant is associated with the following publications: (PMID: 17618893, 12628594, 22993632, 20009762)
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:
p.Ile277Ile in exon 3 of EDNRB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 2.9% (128/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5349).
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Comment:
This variant is associated with the following publications: (PMID: 17618893, 12628594, 22993632, 20009762)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Advances in understanding the association between Down syndrome and Hirschsprung disease (DS-HSCR). | Moore SW | Pediatric surgery international | 2018 | PMID: 30218169 |
| EDNRB gene variants and melanoma risk in two southern European populations. | Spica T | Clinical and experimental dermatology | 2011 | PMID: 21507037 |
| New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. | Sánchez-Mejías A | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20009762 |
| Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension. | Caprioli J | Canadian journal of physiology and pharmacology | 2008 | PMID: 18758497 |
| Down syndrome and the enteric nervous system. | Moore SW | Pediatric surgery international | 2008 | PMID: 18633623 |
| Association of endothelin-beta receptor (EDNRB) gene variants in anorectal malformations. | Moore SW | Journal of pediatric surgery | 2007 | PMID: 17618893 |
| The contribution of associated congenital anomalies in understanding Hirschsprung's disease. | Moore SW | Pediatric surgery international | 2006 | PMID: 16518596 |
| Association between endothelin receptor B nonsynonymous variants and melanoma risk. | Soufir N | Journal of the National Cancer Institute | 2005 | PMID: 16145050 |
| Significance of novel endothelin-B receptor gene polymorphisms in Hirschsprung's disease: predominance of a novel variant (561C/T) in patients with co-existing Down's syndrome. | Zaahl MG | Molecular and cellular probes | 2003 | PMID: 12628594 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=EDNRB | - | - | - | - |
Text-mined citations for rs5349 ...
HelpThese 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
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.