rs7982910

chr13-77909996-T-C

Variant summary

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

The NM_001122659.3(EDNRB):c.484-6389A>G variant causes a intron change. The variant allele was found at a frequency of 0.35 in 151,740 control chromosomes in the GnomAD database, including 11,241 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 0.35 (11241 hom., cov: 31)
• Consequence: EDNRB NM_001122659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_001122659.3	c.484-6389A>G		intron_variant		ENST00000646607.2
EDNRB	NM_000115.5	c.484-6389A>G		intron_variant
EDNRB	NM_001201397.1	c.754-6389A>G		intron_variant
EDNRB	NM_003991.4	c.484-6389A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDNRB	ENST00000646607.2	c.484-6389A>G		intron_variant			NM_001122659.3	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53039 AN: 151622 Hom.: 11242 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.350 AC: 53035 AN: 151740 Hom.: 11241 Cov.: 31 AF XY: 0.342 AC XY: 25369 AN XY: 74168

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.368

Alfa AF: 0.389 Hom.: 1984

Bravo AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	14
Dann	Benign	0.76

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: rs7982910; hg19: chr13-78484131;