rs1239711154

Variant names:

• chr6-12292418-C-G
• NM_001955.5:c.142C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-12292418-C-G
• chr6-12292418-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001955.5(EDN1):​c.142C>G​(p.Arg48Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EDN1 NM_001955.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76

Genes affected

EDN1 (HGNC:3176): (endothelin 1) This gene encodes a preproprotein that is proteolytically processed to generate a secreted peptide that belongs to the endothelin/sarafotoxin family. This peptide is a potent vasoconstrictor and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. Aberrant expression of this gene may promote tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.142C>G	p.Arg48Gly	missense_variant	Exon 2 of 5	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.142C>G	p.Arg48Gly	missense_variant	Exon 2 of 5	1	NM_001955.5	ENSP00000368683.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.44		Loss of helix (P = 0.0068);
MVP		0.92
MPC		0.78
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.48
gMVP		0.86

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: chr6-12292651;