13-77931451-G-C

Variant names:

• chr13-77931451-G-C
• rs9574124
• ENST00000607862.5:n.230+11533G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000607862.5(OBI1-AS1):​n.230+11533G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,848 control chromosomes in the GnomAD database, including 24,288 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 0.56 (24288 hom., cov: 31)
• Consequence: OBI1-AS1 ENST00000607862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 4 publications found

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]

EDNRB Gene-Disease associations (from GenCC):

• ABCD syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Waardenburg syndrome type 4A

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Waardenburg syndrome type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Waardenburg-Shah syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Hirschsprung disease, susceptibility to, 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_000115.5	c.-51-12827C>G		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+11533G>C		intron_variant	Intron 1 of 2	1
EDNRB	ENST00000646948.1	c.-51-12827C>G		intron_variant	Intron 1 of 7			ENSP00000493895.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84497 AN: 151730 Hom.: 24288 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.557 AC: 84518 AN: 151848 Hom.: 24288 Cov.: 31 AF XY: 0.554 AC XY: 41091 AN XY: 74180

African (AFR) AF: 0.414 AC: 17128 AN: 41416

American (AMR) AF: 0.565 AC: 8611 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1943 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2167 AN: 5158

South Asian (SAS) AF: 0.559 AC: 2689 AN: 4812

European-Finnish (FIN) AF: 0.616 AC: 6469 AN: 10500

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.641 AC: 43549 AN: 67932

Other (OTH) AF: 0.563 AC: 1185 AN: 2106

Alfa AF: 0.501 Hom.: 1522

Bravo AF: 0.546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs9574124; hg19: chr13-78505586;