chr20-59300649-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_207034.3(EDN3):c.-164G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 519,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000019 ( 0 hom. )
Consequence
EDN3
NM_207034.3 5_prime_UTR
NM_207034.3 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.785
Publications
0 publications found
Genes affected
EDN3 (HGNC:3178): (endothelin 3) The protein encoded by this gene is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides involved in a variety of biological functions. The active form of this protein is a 21 amino acid peptide processed from the precursor protein. The active peptide is a ligand for endothelin receptor type B (EDNRB). The interaction of this endothelin with EDNRB is essential for development of neural crest-derived cell lineages, such as melanocytes and enteric neurons. Mutations in this gene and EDNRB have been associated with Hirschsprung disease (HSCR) and Waardenburg syndrome (WS), which are congenital disorders involving neural crest-derived cells. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
EDN3 Gene-Disease associations (from GenCC):
- Waardenburg syndromeInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- Waardenburg syndrome type 4BInheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, PanelApp Australia, G2P
- Waardenburg-Shah syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Hirschsprung disease, susceptibility to, 4Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000192 AC: 1AN: 519718Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0AN XY: 272458 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
519718
Hom.:
Cov.:
7
AF XY:
AC XY:
0
AN XY:
272458
show subpopulations
African (AFR)
AF:
AC:
0
AN:
13160
American (AMR)
AF:
AC:
0
AN:
21000
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
14468
East Asian (EAS)
AF:
AC:
0
AN:
30972
South Asian (SAS)
AF:
AC:
0
AN:
48156
European-Finnish (FIN)
AF:
AC:
0
AN:
30552
Middle Eastern (MID)
AF:
AC:
0
AN:
2174
European-Non Finnish (NFE)
AF:
AC:
1
AN:
330872
Other (OTH)
AF:
AC:
0
AN:
28364
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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