13-77920970-A-G

Position:

• chr13-77920970-A-G

Variant summary

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

The ENST00000607862.5(OBI1-AS1):​n.230+1052A>G 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 0.532 in 151,790 control chromosomes in the GnomAD database, including 22,433 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 0.53 (22433 hom., cov: 31)
• Consequence: OBI1-AS1 ENST00000607862.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_000115.5	c.-51-2346T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBI1-AS1	ENST00000607862.5	n.230+1052A>G		intron_variant, non_coding_transcript_variant		1
EDNRB	ENST00000646948.1	c.-51-2346T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80731 AN: 151670 Hom.: 22437 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.532 AC: 80741 AN: 151790 Hom.: 22433 Cov.: 31 AF XY: 0.529 AC XY: 39267 AN XY: 74182

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.526

Alfa AF: 0.583 Hom.: 3173

Bravo AF: 0.520

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3759475; hg19: chr13-78495105;