dbSNP rs2070698: EDN1:c.64+186T>C (chr6-12290879-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.358

Publications

7 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), G2P
auriculocondylar syndrome 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
auriculocondylar syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EDN1 links:

ENSG00000302734 (HGNC:):

ENSG00000302734 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001955.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDN1	NM_001955.5	MANE Select	c.64+186T>C	intron	N/A	NP_001946.3
EDN1	NM_001416563.1		c.64+186T>C	intron	N/A	NP_001403492.1	Q6FH53
EDN1	NM_001416564.1		c.64+186T>C	intron	N/A	NP_001403493.1	Q6FH53

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDN1	ENST00000379375.6	TSL:1 MANE Select	c.64+186T>C	intron	N/A	ENSP00000368683.5	P05305
EDN1	ENST00000877370.1		c.64+186T>C	intron	N/A	ENSP00000547429.1
EDN1	ENST00000971811.1		c.64+186T>C	intron	N/A	ENSP00000641870.1

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75685

AN:

151604

Hom.:

19453

Cov.:

show subpopulations

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.:

AF XY:

0.503

AC XY:

37292

AN XY:

74174

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1905

3810

5714

7619

9524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

686

1372

2058

2744

3430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.519

Hom.:

35657

Bravo

AF:

0.495

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.6

(source)

DANN

Benign

0.68

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over