ENST00000379375:c.-131delA

Variant names:

• chr6-12290495-TA-T
• rs1800997
• NM_001955.5:c.-131delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000379375.6(EDN1):​c.-131delA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (44940 hom., cov: 0)
  • Exomes 𝑓: 0.75 (171476 hom.)
• Consequence: EDN1 ENST00000379375.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 28 publications found

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]

EDN1 Gene-Disease associations (from GenCC):

• question mark ears, isolated

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• auriculocondylar syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379375.6. 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
	EDN1	NM_001955.5	MANE Select	c.-131delA		5_prime_UTR	Exon 1 of 5	NP_001946.3
	EDN1	NM_001168319.2		c.-131delA		5_prime_UTR	Exon 1 of 5	NP_001161791.1
	EDN1	NM_001416563.1		c.-1-130delA		intron	N/A	NP_001403492.1	Q6FH53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDN1	ENST00000379375.6	TSL:1 MANE Select	c.-131delA		5_prime_UTR	Exon 1 of 5	ENSP00000368683.5	P05305
	EDN1	ENST00000877370.1		c.-131delA		5_prime_UTR	Exon 1 of 5	ENSP00000547429.1
	EDN1	ENST00000877373.1		c.-131delA		5_prime_UTR	Exon 1 of 5	ENSP00000547432.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116729 AN: 152102 Hom.: 44887 Cov.: 0

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.754 AC: 451815 AN: 599158 Hom.: 171476 Cov.: 0 AF XY: 0.756 AC XY: 241912 AN XY: 320080

African (AFR) AF: 0.825 AC: 13113 AN: 15894

American (AMR) AF: 0.796 AC: 25246 AN: 31724

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 14050 AN: 19444

East Asian (EAS) AF: 0.851 AC: 27351 AN: 32144

South Asian (SAS) AF: 0.824 AC: 49991 AN: 60672

European-Finnish (FIN) AF: 0.780 AC: 32306 AN: 41416

Middle Eastern (MID) AF: 0.665 AC: 2377 AN: 3576

European-Non Finnish (NFE) AF: 0.727 AC: 263971 AN: 363020

Other (OTH) AF: 0.749 AC: 23410 AN: 31268

GnomAD4 genome AF: 0.768 AC: 116841 AN: 152222 Hom.: 44940 Cov.: 0 AF XY: 0.771 AC XY: 57369 AN XY: 74426

African (AFR) AF: 0.827 AC: 34340 AN: 41544

American (AMR) AF: 0.751 AC: 11495 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2498 AN: 3468

East Asian (EAS) AF: 0.837 AC: 4335 AN: 5178

South Asian (SAS) AF: 0.821 AC: 3965 AN: 4832

European-Finnish (FIN) AF: 0.799 AC: 8464 AN: 10590

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49333 AN: 67992

Other (OTH) AF: 0.736 AC: 1556 AN: 2114

Alfa AF: 0.757 Hom.: 5301

Bravo AF: 0.767

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800997; hg19: chr6-12290728; COSMIC: COSV65080358;