NM_001955.5:c.534-208C>T

Variant names:

• chr6-12295754-C-T
• rs1630736
• NM_001955.5:c.534-208C>T

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.534-208C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,902 control chromosomes in the GnomAD database, including 12,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (12120 hom., cov: 31)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200
• Publications: 21 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 6-12295754-C-T is Benign according to our data. Variant chr6-12295754-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238796.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 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.534-208C>T		intron	N/A	NP_001946.3
	EDN1	NM_001416563.1		c.534-208C>T		intron	N/A	NP_001403492.1	Q6FH53
	EDN1	NM_001416564.1		c.534-208C>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.534-208C>T		intron	N/A	ENSP00000368683.5	P05305
	EDN1	ENST00000877370.1		c.558-208C>T		intron	N/A	ENSP00000547429.1
	EDN1	ENST00000971811.1		c.558-208C>T		intron	N/A	ENSP00000641870.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55276 AN: 151784 Hom.: 12103 Cov.: 31

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55300 AN: 151902 Hom.: 12120 Cov.: 31 AF XY: 0.370 AC XY: 27476 AN XY: 74198

African (AFR) AF: 0.0995 AC: 4125 AN: 41466

American (AMR) AF: 0.447 AC: 6821 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2859 AN: 5146

South Asian (SAS) AF: 0.392 AC: 1893 AN: 4824

European-Finnish (FIN) AF: 0.535 AC: 5612 AN: 10494

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31136 AN: 67946

Other (OTH) AF: 0.387 AC: 815 AN: 2104

Alfa AF: 0.417 Hom.: 2537

Bravo AF: 0.348

Asia WGS AF: 0.459 AC: 1594 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	5.3
DANN	Benign	0.70
PhyloP100		-0.0020
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: rs1630736; hg19: chr6-12295987;