rs17068573

chr13-77927478-G-Achr13-77927478-G-T

Variant summary

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

The ENST00000607862.5(OBI1-AS1):n.230+7560G>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 0.204 in 152,158 control chromosomes in the GnomAD database, including 3,715 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 0.20 (3715 hom., cov: 32)
• Consequence: OBI1-AS1 ENST00000607862.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_000115.5	c.-51-8854C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBI1-AS1	ENST00000607862.5	n.230+7560G>A		intron_variant, non_coding_transcript_variant		1
EDNRB	ENST00000646948.1	c.-51-8854C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30976 AN: 152040 Hom.: 3710 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.204 AC: 31003 AN: 152158 Hom.: 3715 Cov.: 32 AF XY: 0.209 AC XY: 15527 AN XY: 74370

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.193

Alfa AF: 0.109 Hom.: 233

Bravo AF: 0.214

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.7
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17068573; hg19: chr13-78501613;