rs7319342

Variant names:

• chr13-77949349-G-A
• rs7319342
• ENST00000607862.5:n.230+29431G>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+29431G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,008 control chromosomes in the GnomAD database, including 28,037 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 0.59 (28037 hom., cov: 31)
• Consequence: OBI1-AS1 ENST00000607862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_000115.5	c.-52+25998C>T		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+29431G>A		intron_variant	Intron 1 of 2	1
EDNRB	ENST00000646948.1	c.-52+25998C>T		intron_variant	Intron 1 of 7			ENSP00000493895.1
ENSG00000233379	ENST00000435281.2	n.70-4476C>T		intron_variant	Intron 1 of 2	5
ENSG00000233379	ENST00000662890.1	n.66-4476C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90068 AN: 151890 Hom.: 28041 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.593 AC: 90074 AN: 152008 Hom.: 28037 Cov.: 31 AF XY: 0.589 AC XY: 43782 AN XY: 74320

African (AFR) AF: 0.418 AC: 17335 AN: 41448

American (AMR) AF: 0.591 AC: 9022 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1737 AN: 5162

South Asian (SAS) AF: 0.619 AC: 2981 AN: 4814

European-Finnish (FIN) AF: 0.649 AC: 6863 AN: 10568

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47818 AN: 67956

Other (OTH) AF: 0.594 AC: 1253 AN: 2110

Alfa AF: 0.664 Hom.: 28403

Bravo AF: 0.581

Asia WGS AF: 0.507 AC: 1764 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.41
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs7319342; hg19: chr13-78523484;