rs1800542

Variant names:

• chr6-12292295-G-A
• rs1800542
• NM_001955.5:c.65-46G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001955.5(EDN1):​c.65-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,609,308 control chromosomes in the GnomAD database, including 4,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1630 hom., cov: 33)
  • Exomes 𝑓: 0.049 (3026 hom.)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.412
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-12292295-G-A is Benign according to our data. Variant chr6-12292295-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001955.5. 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.65-46G>A		intron	N/A	NP_001946.3
	EDN1	NM_001416563.1		c.65-46G>A		intron	N/A	NP_001403492.1	Q6FH53
	EDN1	NM_001416564.1		c.65-46G>A		intron	N/A	NP_001403493.1	Q6FH53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDN1	ENST00000379375.6	TSL:1 MANE Select	c.65-46G>A		intron	N/A	ENSP00000368683.5	P05305
	EDN1	ENST00000877370.1		c.65-46G>A		intron	N/A	ENSP00000547429.1
	EDN1	ENST00000971811.1		c.65-46G>A		intron	N/A	ENSP00000641870.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15775 AN: 152116 Hom.: 1625 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0980

GnomAD2 exomes AF: 0.0557 AC: 13722 AN: 246412 AF XY: 0.0531

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.0352

Gnomad ASJ exome AF: 0.0585

Gnomad EAS exome AF: 0.00104

Gnomad FIN exome AF: 0.0193

Gnomad NFE exome AF: 0.0443

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0492 AC: 71664 AN: 1457074 Hom.: 3026 Cov.: 32 AF XY: 0.0489 AC XY: 35489 AN XY: 725098

African (AFR) AF: 0.285 AC: 9536 AN: 33476

American (AMR) AF: 0.0374 AC: 1672 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0586 AC: 1531 AN: 26128

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39692

South Asian (SAS) AF: 0.0586 AC: 5053 AN: 86166

European-Finnish (FIN) AF: 0.0214 AC: 1064 AN: 49770

Middle Eastern (MID) AF: 0.0846 AC: 488 AN: 5766

European-Non Finnish (NFE) AF: 0.0439 AC: 48725 AN: 1111014

Other (OTH) AF: 0.0592 AC: 3571 AN: 60338

GnomAD4 genome AF: 0.104 AC: 15800 AN: 152234 Hom.: 1630 Cov.: 33 AF XY: 0.0999 AC XY: 7440 AN XY: 74440

African (AFR) AF: 0.267 AC: 11097 AN: 41490

American (AMR) AF: 0.0588 AC: 900 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5194

South Asian (SAS) AF: 0.0579 AC: 279 AN: 4818

European-Finnish (FIN) AF: 0.0176 AC: 187 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0422 AC: 2871 AN: 68022

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.0799 Hom.: 1764

Bravo AF: 0.113

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.80
PhyloP100		-0.41
Mutation Taster		=100/0	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: rs1800542; hg19: chr6-12292528;