13-77919609-T-C

Variant names:

• chr13-77919609-T-C
• rs876657805
• ENST00000377211.8:c.7A>G
• EDNRB p.Lys3Glu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001201397.2(EDNRB):​c.7A>G​(p.Lys3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EDNRB NM_001201397.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668
• Publications: 0 publications found

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]

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17354032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201397.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	NM_001201397.2		c.7A>G	p.Lys3Glu	missense	Exon 1 of 8	NP_001188326.1	P24530-3
	EDNRB	NM_000115.5		c.-51-985A>G		intron	N/A	NP_000106.1	P24530-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	ENST00000377211.8	TSL:1	c.7A>G	p.Lys3Glu	missense	Exon 1 of 8	ENSP00000366416.4	P24530-3
	EDNRB	ENST00000646948.1		c.-51-985A>G		intron	N/A	ENSP00000493895.1	P24530-1
	OBI1-AS1	ENST00000607862.5	TSL:1	n.-80T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.29	T
PhyloP100		0.67
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
PromoterAI		-0.043	Neutral
gMVP		0.16
Mutation Taster		=82/18	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs876657805;

hg19: chr13-78493744;