chr13-77954099-C-T

Position:

• chr13-77954099-C-T

Variant summary

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

The ENST00000435281.2(ENSG00000233379):​n.70-9226G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,210 control chromosomes in the GnomAD database, including 577 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 0.074 (577 hom., cov: 32)
• Consequence: ENST00000435281.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

Genes affected

(HGNC:):

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_000115.5	c.-52+21248G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000435281.2	n.70-9226G>A		intron_variant, non_coding_transcript_variant		5
OBI1-AS1	ENST00000607862.5	n.230+34181C>T		intron_variant, non_coding_transcript_variant		1
EDNRB	ENST00000646948.1	c.-52+21248G>A		intron_variant				P1
	ENST00000662890.1	n.66-9226G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11275 AN: 152092 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0733

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

GnomAD4 genome AF: 0.0740 AC: 11271 AN: 152210 Hom.: 577 Cov.: 32 AF XY: 0.0707 AC XY: 5259 AN XY: 74424

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0725

Alfa AF: 0.0959 Hom.: 114

Bravo AF: 0.0718

Asia WGS AF: 0.0120 AC: 40 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1537063; hg19: chr13-78528234;