chr13-77948179-G-A

Variant names:

• chr13-77948179-G-A
• rs1924914
• ENST00000607862.5:n.230+28261G>A

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+28261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,058 control chromosomes in the GnomAD database, including 33,359 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 0.66 (33359 hom., cov: 32)
• Consequence: OBI1-AS1 ENST00000607862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 3 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)

ENSG00000233379 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607862.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	NM_000115.5		c.-52+27168C>T		intron	N/A	NP_000106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBI1-AS1	ENST00000607862.5	TSL:1	n.230+28261G>A		intron	N/A
	EDNRB	ENST00000646948.1		c.-52+27168C>T		intron	N/A	ENSP00000493895.1
	ENSG00000233379	ENST00000435281.2	TSL:5	n.70-3306C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99575 AN: 151940 Hom.: 33355 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.655 AC: 99612 AN: 152058 Hom.: 33359 Cov.: 32 AF XY: 0.653 AC XY: 48545 AN XY: 74322

African (AFR) AF: 0.532 AC: 22084 AN: 41480

American (AMR) AF: 0.632 AC: 9648 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2427 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2306 AN: 5152

South Asian (SAS) AF: 0.676 AC: 3251 AN: 4810

European-Finnish (FIN) AF: 0.713 AC: 7550 AN: 10588

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50023 AN: 67980

Other (OTH) AF: 0.667 AC: 1407 AN: 2110

Alfa AF: 0.710 Hom.: 4810

Bravo AF: 0.642

Asia WGS AF: 0.603 AC: 2097 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.51
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs1924914; hg19: chr13-78522314;