rs11618814

Variant names:

• chr13-77930639-C-T
• rs11618814
• ENST00000607862.5:n.230+10721C>T

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+10721C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• 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=-0.82).
• 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 rank	MANE	Protein	UniProt
EDNRB	NM_000115.5	c.-51-12015G>A		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+10721C>T		intron_variant	Intron 1 of 2	1
EDNRB	ENST00000646948.1	c.-51-12015G>A		intron_variant	Intron 1 of 7			ENSP00000493895.1

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

African (AFR) AF: 0.0133 AC: 552 AN: 41560

American (AMR) AF: 0.0740 AC: 1133 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3472

East Asian (EAS) AF: 0.0243 AC: 126 AN: 5182

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4826

European-Finnish (FIN) AF: 0.0494 AC: 524 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4415 AN: 68008

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0502 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
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11618814; hg19: chr13-78504774;