13-77967486-A-C

Position:

• chr13-77967486-A-C

Variant summary

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

The NM_000115.5(EDNRB):​c.-52+7861T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,052 control chromosomes in the GnomAD database, including 5,831 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 0.25 (5831 hom., cov: 32)
• Consequence: EDNRB NM_000115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

OBI1-AS1 (HGNC:):

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRB	NM_000115.5	c.-52+7861T>G		intron_variant			NP_000106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBI1-AS1	ENST00000607862.5	n.230+47568A>C		intron_variant		1
EDNRB	ENST00000646948.1	c.-52+7861T>G		intron_variant				ENSP00000493895.1
ENSG00000233379	ENST00000435281.2	n.69+7985T>G		intron_variant		5
ENSG00000233379	ENST00000662890.1	n.65+7861T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37595 AN: 151934 Hom.: 5806 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.248 AC: 37668 AN: 152052 Hom.: 5831 Cov.: 32 AF XY: 0.251 AC XY: 18647 AN XY: 74326

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.228

Alfa AF: 0.170 Hom.: 5204

Bravo AF: 0.264

Asia WGS AF: 0.331 AC: 1151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4884075; hg19: chr13-78541621;