chr6-12295643-A-G

Variant names:

• chr6-12295643-A-G
• rs1629862
• NM_001955.5:c.534-319A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001955.5(EDN1):​c.534-319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,142 control chromosomes in the GnomAD database, including 60,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60165 hom., cov: 31)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 15 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: G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302734 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.534-319A>G		intron_variant	Intron 4 of 4	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.534-319A>G		intron_variant	Intron 4 of 4	1	NM_001955.5	ENSP00000368683.5

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135207 AN: 152024 Hom.: 60133 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.889 AC: 135298 AN: 152142 Hom.: 60165 Cov.: 31 AF XY: 0.893 AC XY: 66412 AN XY: 74372

African (AFR) AF: 0.876 AC: 36356 AN: 41494

American (AMR) AF: 0.907 AC: 13872 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3080 AN: 3470

East Asian (EAS) AF: 0.974 AC: 5033 AN: 5166

South Asian (SAS) AF: 0.948 AC: 4573 AN: 4822

European-Finnish (FIN) AF: 0.912 AC: 9648 AN: 10582

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

European-Non Finnish (NFE) AF: 0.881 AC: 59888 AN: 68000

Other (OTH) AF: 0.884 AC: 1868 AN: 2112

Alfa AF: 0.886 Hom.: 38904

Bravo AF: 0.886

Asia WGS AF: 0.933 AC: 3244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.27
PhyloP100		-1.5
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: rs1629862; hg19: chr6-12295876;