13-77912266-C-T

Variant names:

• chr13-77912266-C-T
• rs3027129
• NM_001122659.3:c.483+5825G>A

Variant summary

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

The NM_001122659.3(EDNRB):​c.483+5825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,138 control chromosomes in the GnomAD database, including 287 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 0.051 (287 hom., cov: 32)
• Consequence: EDNRB NM_001122659.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_001122659.3	c.483+5825G>A		intron_variant	Intron 1 of 6	ENST00000646607.2	NP_001116131.1
EDNRB	NM_001201397.2	c.753+5825G>A		intron_variant	Intron 2 of 7		NP_001188326.1
EDNRB	NM_000115.5	c.483+5825G>A		intron_variant	Intron 2 of 7		NP_000106.1
EDNRB	NM_003991.4	c.483+5825G>A		intron_variant	Intron 1 of 6		NP_003982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000646607.2	c.483+5825G>A		intron_variant	Intron 1 of 6		NM_001122659.3	ENSP00000493527.1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7772 AN: 152020 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0537

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

GnomAD4 genome AF: 0.0510 AC: 7766 AN: 152138 Hom.: 287 Cov.: 32 AF XY: 0.0486 AC XY: 3618 AN XY: 74378

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.0799

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0470 Hom.: 68

Bravo AF: 0.0470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.67

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: rs3027129; hg19: chr13-78486401;