rs4885493

Positions:

• chr13-77908928-C-G

Variant summary

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

The NM_001122659.3(EDNRB):​c.484-5321G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,872 control chromosomes in the GnomAD database, including 9,835 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 0.34 (9835 hom., cov: 33)
• Consequence: EDNRB NM_001122659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

Genes affected

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_001122659.3	c.484-5321G>C		intron_variant		ENST00000646607.2
EDNRB	NM_000115.5	c.484-5321G>C		intron_variant
EDNRB	NM_001201397.1	c.754-5321G>C		intron_variant
EDNRB	NM_003991.4	c.484-5321G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDNRB	ENST00000646607.2	c.484-5321G>C		intron_variant			NM_001122659.3	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52251 AN: 151752 Hom.: 9822 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.344 AC: 52304 AN: 151872 Hom.: 9835 Cov.: 33 AF XY: 0.349 AC XY: 25884 AN XY: 74220

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.336

Alfa AF: 0.299 Hom.: 919

Bravo AF: 0.355

Asia WGS AF: 0.442 AC: 1536 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4885493; hg19: chr13-78483063;