rs12585038

Variant names:

• chr13-77906440-G-A
• rs12585038
• NM_001122659.3:c.484-2833C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122659.3(EDNRB):​c.484-2833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,994 control chromosomes in the GnomAD database, including 2,682 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 0.17 (2682 hom., cov: 33)
• Consequence: EDNRB NM_001122659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 3 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]

EDNRB-AS1 (HGNC:49045): (EDNRB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_001122659.3	c.484-2833C>T		intron_variant	Intron 1 of 6	ENST00000646607.2	NP_001116131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000646607.2	c.484-2833C>T		intron_variant	Intron 1 of 6		NM_001122659.3	ENSP00000493527.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25920 AN: 151876 Hom.: 2681 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.171 AC: 25930 AN: 151994 Hom.: 2682 Cov.: 33 AF XY: 0.177 AC XY: 13127 AN XY: 74296

African (AFR) AF: 0.138 AC: 5744 AN: 41490

American (AMR) AF: 0.238 AC: 3633 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3464

East Asian (EAS) AF: 0.534 AC: 2741 AN: 5132

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1818 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9919 AN: 67916

Other (OTH) AF: 0.160 AC: 337 AN: 2108

Alfa AF: 0.145 Hom.: 225

Bravo AF: 0.176

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.43
DANN	Benign	0.58
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12585038; hg19: chr13-78480575;