chr6-12295754-C-T

Position:

• chr6-12295754-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-208C>T		intron_variant		ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.534-208C>T		intron_variant		1	NM_001955.5	ENSP00000368683.5

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

Gnomad4 AFR AF: 0.0995

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.387

Alfa AF: 0.417 Hom.: 2537

Bravo AF: 0.348

Asia WGS AF: 0.459 AC: 1594 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

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.70

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: rs1630736; hg19: chr6-12295987;