13-77925434-C-T

Variant names:

• chr13-77925434-C-T
• rs9544636
• ENST00000607862.5:n.230+5516C>T

Variant summary

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

The NM_000115.5(EDNRB):​c.-51-6810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,170 control chromosomes in the GnomAD database, including 884 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 0.10 (884 hom., cov: 33)
• Consequence: EDNRB NM_000115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

Genes affected

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_000115.5	c.-51-6810G>A		intron_variant	Intron 1 of 7		NP_000106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBI1-AS1	ENST00000607862.5	n.230+5516C>T		intron_variant	Intron 1 of 2	1
EDNRB	ENST00000646948.1	c.-51-6810G>A		intron_variant	Intron 1 of 7			ENSP00000493895.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15572 AN: 152052 Hom.: 880 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.102 AC: 15589 AN: 152170 Hom.: 884 Cov.: 33 AF XY: 0.102 AC XY: 7557 AN XY: 74392

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0879

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0980 Hom.: 1051

Bravo AF: 0.105

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.1
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9544636; hg19: chr13-78499569;