rs3027111

Positions:

• chr13-77907733-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122659.3(EDNRB):​c.484-4126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,504 control chromosomes in the GnomAD database, including 4,025 homozygotes. 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: 𝑓 0.22 (4025 hom., cov: 31)
• Consequence: EDNRB NM_001122659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRB	NM_001122659.3	c.484-4126G>A		intron_variant		ENST00000646607.2	NP_001116131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000646607.2	c.484-4126G>A		intron_variant			NM_001122659.3	ENSP00000493527.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32643 AN: 151386 Hom.: 4021 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.216 AC: 32669 AN: 151504 Hom.: 4025 Cov.: 31 AF XY: 0.222 AC XY: 16429 AN XY: 74010

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.198

Alfa AF: 0.178 Hom.: 2343

Bravo AF: 0.221

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.33

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: rs3027111; hg19: chr13-78481868;