rs11618814

chr13-77930639-C-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+10721C>T 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 0.0472 in 152,270 control chromosomes in the GnomAD database, including 225 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 0.047 (225 hom., cov: 33)
• Consequence: OBI1-AS1 ENST00000607862.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_000115.5	c.-51-12015G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBI1-AS1	ENST00000607862.5	n.230+10721C>T		intron_variant, non_coding_transcript_variant		1
EDNRB	ENST00000646948.1	c.-51-12015G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7191 AN: 152152 Hom.: 225 Cov.: 33

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0472 AC: 7193 AN: 152270 Hom.: 225 Cov.: 33 AF XY: 0.0472 AC XY: 3513 AN XY: 74460

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.0243

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0649

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0515 Hom.: 24

Bravo AF: 0.0485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.4
Dann	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11618814; hg19: chr13-78504774;