chr13-77896356-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001122659.3(EDNRB):c.*1844A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000569 in 1,424,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 1 hom. )
Consequence
EDNRB
NM_001122659.3 3_prime_UTR
NM_001122659.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.496
Genes affected
EDNRB (HGNC:3180): (endothelin receptor type B) The protein encoded by this gene is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. Studies suggest that the multigenic disorder, Hirschsprung disease type 2, is due to mutations in the endothelin receptor type B gene. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDNRB | NM_001122659.3 | c.*1844A>G | 3_prime_UTR_variant | 7/7 | ENST00000646607.2 | ||
EDNRB-AS1 | NR_103853.1 | n.1695-11336T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDNRB | ENST00000646607.2 | c.*1844A>G | 3_prime_UTR_variant | 7/7 | NM_001122659.3 | P1 | |||
EDNRB | ENST00000377211.8 | c.*1844A>G | 3_prime_UTR_variant | 8/8 | 1 | ||||
EDNRB | ENST00000646605.1 | c.*1844A>G | 3_prime_UTR_variant | 8/8 | P1 | ||||
EDNRB | ENST00000646948.1 | c.*1844A>G | 3_prime_UTR_variant | 8/8 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152002Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
8
AN:
152002
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000574 AC: 73AN: 1272352Hom.: 1 Cov.: 18 AF XY: 0.0000684 AC XY: 43AN XY: 628780
GnomAD4 exome
AF:
AC:
73
AN:
1272352
Hom.:
Cov.:
18
AF XY:
AC XY:
43
AN XY:
628780
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152002Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5AN XY: 74228
GnomAD4 genome
AF:
AC:
8
AN:
152002
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74228
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hirschsprung disease, susceptibility to, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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