rs17068573

Variant names:

• chr13-77927478-G-A
• rs17068573
• ENST00000607862.5:n.230+7560G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-77927478-G-A
• chr13-77927478-G-T

Variant summary

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

The NM_000115.5(EDNRB):​c.-51-8854C>T variant causes a intron 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: EDNRB NM_000115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• 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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000115.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	NM_000115.5		c.-51-8854C>T		intron	N/A	NP_000106.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBI1-AS1	ENST00000607862.5	TSL:1	n.230+7560G>A		intron	N/A
	EDNRB	ENST00000646948.1		c.-51-8854C>T		intron	N/A	ENSP00000493895.1

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

African (AFR) AF: 0.252 AC: 10460 AN: 41502

American (AMR) AF: 0.255 AC: 3900 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3472

East Asian (EAS) AF: 0.529 AC: 2737 AN: 5174

South Asian (SAS) AF: 0.253 AC: 1217 AN: 4818

European-Finnish (FIN) AF: 0.172 AC: 1818 AN: 10578

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9930 AN: 68002

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.113 Hom.: 253

Bravo AF: 0.214

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.46
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs17068573; hg19: chr13-78501613;