rs1801710

Variant names:

• chr13-77918405-C-G
• NM_001122659.3:c.169G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-77918405-C-G
• chr13-77918405-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2 PM5 BP4_Strong

The NM_001122659.3(EDNRB):​c.169G>C​(p.Gly57Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G57S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EDNRB NM_001122659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr13-77918405-C-T is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.060347766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_001122659.3	c.169G>C	p.Gly57Arg	missense_variant	Exon 1 of 7	ENST00000646607.2	NP_001116131.1
EDNRB	NM_001201397.2	c.439G>C	p.Gly147Arg	missense_variant	Exon 2 of 8		NP_001188326.1
EDNRB	NM_000115.5	c.169G>C	p.Gly57Arg	missense_variant	Exon 2 of 8		NP_000106.1
EDNRB	NM_003991.4	c.169G>C	p.Gly57Arg	missense_variant	Exon 1 of 7		NP_003982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000646607.2	c.169G>C	p.Gly57Arg	missense_variant	Exon 1 of 7		NM_001122659.3	ENSP00000493527.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.5
DANN	Benign	0.85
DEOGEN2	Benign	0.28	.;T;T;T;T;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.71	T;.;.;.;.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.060	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L;L;L;L;L;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.44	N;.;.;N;.;.;.;.
REVEL	Benign	0.013
Sift	Benign	0.030	D;.;.;T;.;.;.;.
Sift4G	Benign	0.065	T;.;.;T;.;T;.;.
Polyphen		0.013	B;B;B;B;B;B;B;.
Vest4		0.089
MutPred		0.34		.;Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);Gain of MoRF binding (P = 0.0189);
MVP		0.38
MPC		0.55
ClinPred		0.089	T
GERP RS		-0.44
Varity_R		0.11
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-78492540;