rs1924914

Positions:

• chr13-77948179-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435281.2(ENSG00000233379):​n.70-3306C>T variant causes a intron, non coding transcript 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: ENST00000435281.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRB	NM_000115.5	c.-52+27168C>T		intron_variant			NP_000106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000435281.2	n.70-3306C>T		intron_variant, non_coding_transcript_variant		5
OBI1-AS1	ENST00000607862.5	n.230+28261G>A		intron_variant, non_coding_transcript_variant		1
EDNRB	ENST00000646948.1	c.-52+27168C>T		intron_variant				ENSP00000493895	P1
	ENST00000662890.1	n.66-3306C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.667

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1924914; hg19: chr13-78522314;