13-77896215-A-G

Position:

• chr13-77896215-A-G

Variant summary

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

The NM_001122659.3(EDNRB):​c.*1985T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 242,920 control chromosomes in the GnomAD database, including 97,219 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 0.90 (60989 hom., cov: 31)
  • Exomes 𝑓: 0.89 (36230 hom.)
• Consequence: EDNRB NM_001122659.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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]

EDNRB-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRB	NM_001122659.3	c.*1985T>C		3_prime_UTR_variant	7/7	ENST00000646607.2
EDNRB-AS1	NR_103853.1	n.1695-11477A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDNRB	ENST00000646607.2	c.*1985T>C		3_prime_UTR_variant	7/7		NM_001122659.3	P1
EDNRB	ENST00000377211.8	c.*1985T>C		3_prime_UTR_variant	8/8	1
EDNRB	ENST00000646605.1	c.*1985T>C		3_prime_UTR_variant	8/8			P1
EDNRB	ENST00000646948.1	c.*1985T>C		3_prime_UTR_variant	8/8			P1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 135924 AN: 151734 Hom.: 60944 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.892

GnomAD4 exome AF: 0.892 AC: 81215 AN: 91070 Hom.: 36230 Cov.: 3 AF XY: 0.891 AC XY: 43510 AN XY: 48840

Gnomad4 AFR exome AF: 0.914

Gnomad4 AMR exome AF: 0.913

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.935

Gnomad4 FIN exome AF: 0.887

Gnomad4 NFE exome AF: 0.884

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.896 AC: 136025 AN: 151850 Hom.: 60989 Cov.: 31 AF XY: 0.897 AC XY: 66576 AN XY: 74218

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.888

Alfa AF: 0.881 Hom.: 55630

Bravo AF: 0.898

Asia WGS AF: 0.928 AC: 3190 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.50

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: rs4885491; hg19: chr13-78470350;