rs2070699

Variant names:

• chr6-12292539-G-T
• rs2070699
• NM_001955.5:c.233+30G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-12292539-G-T
• chr6-12292539-G-C

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.233+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,612,970 control chromosomes in the GnomAD database, including 169,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (12380 hom., cov: 33)
  • Exomes 𝑓: 0.46 (156829 hom.)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.267
• Publications: 64 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=-0.79).
• BP6: Variant 6-12292539-G-T is Benign according to our data. Variant chr6-12292539-G-T is described in ClinVar as Benign. ClinVar VariationId is 1274781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 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.233+30G>T		intron	N/A	NP_001946.3
	EDN1	NM_001416563.1		c.233+30G>T		intron	N/A	NP_001403492.1	Q6FH53
	EDN1	NM_001416564.1		c.233+30G>T		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.233+30G>T		intron	N/A	ENSP00000368683.5	P05305
	EDN1	ENST00000877370.1		c.233+30G>T		intron	N/A	ENSP00000547429.1
	EDN1	ENST00000971811.1		c.233+30G>T		intron	N/A	ENSP00000641870.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55731 AN: 152000 Hom.: 12367 Cov.: 33

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.385

GnomAD2 exomes AF: 0.451 AC: 113343 AN: 251142 AF XY: 0.454

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.424

Gnomad EAS exome AF: 0.547

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.458 AC: 668873 AN: 1460854 Hom.: 156829 Cov.: 35 AF XY: 0.457 AC XY: 332213 AN XY: 726790

African (AFR) AF: 0.0783 AC: 2619 AN: 33464

American (AMR) AF: 0.515 AC: 23010 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 11143 AN: 26134

East Asian (EAS) AF: 0.541 AC: 21458 AN: 39686

South Asian (SAS) AF: 0.404 AC: 34830 AN: 86240

European-Finnish (FIN) AF: 0.537 AC: 28705 AN: 53412

Middle Eastern (MID) AF: 0.383 AC: 2211 AN: 5766

European-Non Finnish (NFE) AF: 0.467 AC: 518588 AN: 1111104

Other (OTH) AF: 0.436 AC: 26309 AN: 60346

GnomAD4 genome AF: 0.366 AC: 55743 AN: 152116 Hom.: 12380 Cov.: 33 AF XY: 0.374 AC XY: 27780 AN XY: 74364

African (AFR) AF: 0.0957 AC: 3974 AN: 41524

American (AMR) AF: 0.449 AC: 6873 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2806 AN: 5160

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4820

European-Finnish (FIN) AF: 0.556 AC: 5886 AN: 10580

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31403 AN: 67954

Other (OTH) AF: 0.391 AC: 824 AN: 2110

Alfa AF: 0.420 Hom.: 22407

Bravo AF: 0.349

Asia WGS AF: 0.456 AC: 1582 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	-0.79
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.27
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: rs2070699; hg19: chr6-12292772; COSMIC: COSV65080425;