rs5369

Variant names:

• chr6-12294025-A-G
• rs5369
• NM_001955.5:c.318A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-12294025-A-G
• chr6-12294025-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001955.5(EDN1):​c.318A>G​(p.Glu106Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,614,152 control chromosomes in the GnomAD database, including 636,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59329 hom., cov: 33)
  • Exomes 𝑓: 0.89 (576812 hom.)
• Consequence: EDN1 NM_001955.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.442
• Publications: 57 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-12294025-A-G is Benign according to our data. Variant chr6-12294025-A-G is described in ClinVar as Benign. ClinVar VariationId is 1255370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.442 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 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.318A>G	p.Glu106Glu	synonymous	Exon 3 of 5	NP_001946.3
	EDN1	NM_001416563.1		c.318A>G	p.Glu106Glu	synonymous	Exon 4 of 6	NP_001403492.1	Q6FH53
	EDN1	NM_001416564.1		c.318A>G	p.Glu106Glu	synonymous	Exon 4 of 6	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.318A>G	p.Glu106Glu	synonymous	Exon 3 of 5	ENSP00000368683.5	P05305
	EDN1	ENST00000877370.1		c.342A>G	p.Glu114Glu	synonymous	Exon 3 of 5	ENSP00000547429.1
	EDN1	ENST00000971811.1		c.342A>G	p.Glu114Glu	synonymous	Exon 5 of 7	ENSP00000641870.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134308 AN: 152168 Hom.: 59299 Cov.: 33

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.879

GnomAD2 exomes AF: 0.904 AC: 227390 AN: 251448 AF XY: 0.905

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.931

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.976

Gnomad FIN exome AF: 0.913

Gnomad NFE exome AF: 0.879

Gnomad OTH exome AF: 0.884

GnomAD4 exome AF: 0.888 AC: 1297864 AN: 1461866 Hom.: 576812 Cov.: 65 AF XY: 0.890 AC XY: 646907 AN XY: 727236

African (AFR) AF: 0.852 AC: 28519 AN: 33480

American (AMR) AF: 0.927 AC: 41476 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 23297 AN: 26134

East Asian (EAS) AF: 0.977 AC: 38778 AN: 39698

South Asian (SAS) AF: 0.952 AC: 82110 AN: 86258

European-Finnish (FIN) AF: 0.914 AC: 48795 AN: 53414

Middle Eastern (MID) AF: 0.863 AC: 4976 AN: 5768

European-Non Finnish (NFE) AF: 0.878 AC: 976270 AN: 1111994

Other (OTH) AF: 0.888 AC: 53643 AN: 60396

GnomAD4 genome AF: 0.883 AC: 134396 AN: 152286 Hom.: 59329 Cov.: 33 AF XY: 0.886 AC XY: 65991 AN XY: 74468

African (AFR) AF: 0.853 AC: 35464 AN: 41558

American (AMR) AF: 0.905 AC: 13838 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3081 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5049 AN: 5182

South Asian (SAS) AF: 0.946 AC: 4565 AN: 4826

European-Finnish (FIN) AF: 0.912 AC: 9668 AN: 10606

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59893 AN: 68026

Other (OTH) AF: 0.880 AC: 1858 AN: 2112

Alfa AF: 0.880 Hom.: 126357

Bravo AF: 0.878

Asia WGS AF: 0.928 AC: 3225 AN: 3478

EpiCase AF: 0.867

EpiControl AF: 0.869

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Auriculocondylar syndrome 3 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		0.44
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: rs5369; hg19: chr6-12294258; COSMIC: COSV108234603;