rs1800541

Variant names:

• chr6-12288986-T-G
• rs1800541
• NM_001416564.1:c.-2+912T>G

Variant summary

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

The NM_001416564.1(EDN1):​c.-2+912T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,004 control chromosomes in the GnomAD database, including 5,109 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 0.24 (5109 hom., cov: 32)
• Consequence: EDN1 NM_001416564.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 47 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001416564.1	c.-2+912T>G		intron_variant	Intron 1 of 5		NP_001403493.1
EDN1	NM_001416565.1	c.-1-1643T>G		intron_variant	Intron 3 of 7		NP_001403494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302734	ENST00000789282.1	n.70+22195A>C		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.*85A>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36414 AN: 151886 Hom.: 5100 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.240 AC: 36456 AN: 152004 Hom.: 5109 Cov.: 32 AF XY: 0.242 AC XY: 18003 AN XY: 74282

African (AFR) AF: 0.385 AC: 15927 AN: 41392

American (AMR) AF: 0.162 AC: 2478 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5162

South Asian (SAS) AF: 0.340 AC: 1635 AN: 4814

European-Finnish (FIN) AF: 0.214 AC: 2267 AN: 10592

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11831 AN: 67974

Other (OTH) AF: 0.211 AC: 444 AN: 2106

Alfa AF: 0.236 Hom.: 708

Bravo AF: 0.238

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.54
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800541; hg19: chr6-12289219;