Variant rs2229450 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001397.3(ECE1):c.1155C>T(p.Thr385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,613,978 control chromosomes in the GnomAD database, including 51,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3674 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47655 hom. )

Consequence

ECE1
NM_001397.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.05

Variant links:

Genes affected

ECE1 (HGNC:3146): (endothelin converting enzyme 1) The protein encoded by this gene is involved in proteolytic processing of endothelin precursors to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Sep 2009]

ECE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-21247229-G-A is Benign according to our data. Variant chr1-21247229-G-A is described in ClinVar as [Benign]. Clinvar id is 258080.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECE1	NM_001397.3 linkuse as main transcript	c.1155C>T	p.Thr385=	synonymous_variant	9/19	ENST00000374893.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECE1	ENST00000374893.11 linkuse as main transcript	c.1155C>T	p.Thr385=	synonymous_variant	9/19	1	NM_001397.3		P42892-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29880

AN:

152084

Hom.:

3676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0522

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.222

AC:

55757

AN:

251464

Hom.:

6823

AF XY:

0.224

AC XY:

30465

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0483

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.250

AC:

365674

AN:

1461778

Hom.:

47655

Cov.:

AF XY:

0.248

AC XY:

180415

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0474

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.196

AC:

29879

AN:

152200

Hom.:

3674

Cov.:

AF XY:

0.193

AC XY:

14375

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0521

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.240

Hom.:

2407

Bravo

AF:

0.188

Asia WGS

AF:

0.136

AC:

476

AN:

3478

EpiCase

AF:

0.255

EpiControl

AF:

0.270

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.092

DANN

Benign

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over