6-12290879-T-C

Variant names:

• chr6-12290879-T-C
• rs2070698
• NM_001955.5:c.64+186T>C

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.64+186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,724 control chromosomes in the GnomAD database, including 19,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19481 hom., cov: 33)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.358
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-12290879-T-C is Benign according to our data. Variant chr6-12290879-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDN1	NM_001955.5	c.64+186T>C		intron_variant	Intron 1 of 4	ENST00000379375.6	NP_001946.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDN1	ENST00000379375.6	c.64+186T>C		intron_variant	Intron 1 of 4	1	NM_001955.5	ENSP00000368683.5
ENSG00000302734	ENST00000789282.1	n.70+20302A>G		intron_variant	Intron 1 of 3
ENSG00000302734	ENST00000789283.1	n.26-83A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75685 AN: 151604 Hom.: 19453 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.499 AC: 75747 AN: 151724 Hom.: 19481 Cov.: 33 AF XY: 0.503 AC XY: 37292 AN XY: 74174

African (AFR) AF: 0.369 AC: 15284 AN: 41426

American (AMR) AF: 0.579 AC: 8829 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1671 AN: 3394

East Asian (EAS) AF: 0.647 AC: 3354 AN: 5182

South Asian (SAS) AF: 0.492 AC: 2371 AN: 4816

European-Finnish (FIN) AF: 0.618 AC: 6522 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36021 AN: 67786

Other (OTH) AF: 0.513 AC: 1081 AN: 2106

Alfa AF: 0.519 Hom.: 35657

Bravo AF: 0.495

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.68
PhyloP100		0.36
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: rs2070698; hg19: chr6-12291112;