chr13-77895737-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001122659.3(EDNRB):c.*2463T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0032 in 152,158 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0032 ( 6 hom., cov: 32)
Failed GnomAD Quality Control
Consequence
EDNRB
NM_001122659.3 3_prime_UTR
NM_001122659.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.18
Publications
1 publications found
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 was made for transcript
Our verdict: Benign. The variant received -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0032 (487/152158) while in subpopulation AMR AF = 0.00413 (63/15266). AF 95% confidence interval is 0.00331. There are 6 homozygotes in GnomAd4. There are 225 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 6 AD,AR,Unknown,SD gene
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001122659.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EDNRB | NM_001122659.3 | MANE Select | c.*2463T>C | 3_prime_UTR | Exon 7 of 7 | NP_001116131.1 | P24530-1 | ||
| EDNRB | NM_001201397.2 | c.*2463T>C | 3_prime_UTR | Exon 8 of 8 | NP_001188326.1 | P24530-3 | |||
| EDNRB | NM_000115.5 | c.*2463T>C | 3_prime_UTR | Exon 8 of 8 | NP_000106.1 | P24530-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EDNRB | ENST00000646607.2 | MANE Select | c.*2463T>C | 3_prime_UTR | Exon 7 of 7 | ENSP00000493527.1 | P24530-1 | ||
| EDNRB | ENST00000377211.8 | TSL:1 | c.*2463T>C | 3_prime_UTR | Exon 8 of 8 | ENSP00000366416.4 | P24530-3 | ||
| EDNRB | ENST00000646605.1 | c.*2463T>C | 3_prime_UTR | Exon 8 of 8 | ENSP00000494278.1 | P24530-1 |
Frequencies
GnomAD3 genomes 0.00322 AC: 490AN: 152040Hom.: 6 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
490
AN:
152040
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 Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
Cov.:
0
AC XY:
0
AN XY:
0
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AC:
0
AN:
0
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome 0.00320 AC: 487AN: 152158Hom.: 6 Cov.: 32 AF XY: 0.00302 AC XY: 225AN XY: 74382 show subpopulations
GnomAD4 genome
AF:
AC:
487
AN:
152158
Hom.:
Cov.:
32
AF XY:
AC XY:
225
AN XY:
74382
show subpopulations
African (AFR)
AF:
AC:
93
AN:
41562
American (AMR)
AF:
AC:
63
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
83
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5158
South Asian (SAS)
AF:
AC:
2
AN:
4828
European-Finnish (FIN)
AF:
AC:
1
AN:
10624
Middle Eastern (MID)
AF:
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
AC:
222
AN:
67932
Other (OTH)
AF:
AC:
10
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
25
50
76
101
126
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
11
AN:
3462
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Hirschsprung disease, susceptibility to, 2 (1)
Computational 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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.