rs3818416

Positions:

• chr13-77900333-A-C
• chr13-77900333-A-G
• chr13-77900333-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001122659.3(EDNRB):​c.1085+188T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 151,704 control chromosomes in the GnomAD database, including 42,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (42780 hom., cov: 31)
• Consequence: EDNRB NM_001122659.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.350

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]

EDNRB-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-77900333-A-C is Benign according to our data. Variant chr13-77900333-A-C is described in ClinVar as [Benign]. Clinvar id is 1246466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRB	NM_001122659.3	c.1085+188T>G		intron_variant		ENST00000646607.2	NP_001116131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000646607.2	c.1085+188T>G		intron_variant			NM_001122659.3	ENSP00000493527.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113514 AN: 151586 Hom.: 42767 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.749 AC: 113569 AN: 151704 Hom.: 42780 Cov.: 31 AF XY: 0.751 AC XY: 55626 AN XY: 74116

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.885

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.731

Alfa AF: 0.755 Hom.: 42269

Bravo AF: 0.749

Asia WGS AF: 0.794 AC: 2760 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3818416; hg19: chr13-78474468;