6-12293922-TTC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001955.5(EDN1):c.234-13_234-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000967 in 1,613,948 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00067 (3 hom.)
• Consequence: EDN1 NM_001955.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0220

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-12293922-TTC-T is Benign according to our data. Variant chr6-12293922-TTC-T is described in ClinVar as [Benign]. Clinvar id is 3020086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5	c.234-13_234-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6	c.234-13_234-12del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001955.5	P1

Frequencies

GnomAD3 genomes AF: 0.00381 AC: 580 AN: 152210 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00134 AC: 335 AN: 249994 Hom.: 2 AF XY: 0.00107 AC XY: 145 AN XY: 135444

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000434

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000670 AC: 980 AN: 1461620 Hom.: 3 AF XY: 0.000598 AC XY: 435 AN XY: 727130

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.00153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000304

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00381 AC: 580 AN: 152328 Hom.: 3 Cov.: 33 AF XY: 0.00357 AC XY: 266 AN XY: 74480

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00265 Hom.: 1

Bravo AF: 0.00464

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs10478721; hg19: chr6-12294155;