Variant rs28368004 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001397.3(ECE1):c.1278+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 1,612,874 control chromosomes in the GnomAD database, including 966 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 84 hom., cov: 32)

Exomes 𝑓: 0.031 ( 882 hom. )

Consequence

ECE1
NM_001397.3 splice_region, intron

Scores

Splicing: ADA: 0.0002036

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.26

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-21244982-G-A is Benign according to our data. Variant chr1-21244982-G-A is described in ClinVar as [Benign]. Clinvar id is 258082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-21244982-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3626/152282) while in subpopulation NFE AF= 0.0353 (2401/68016). AF 95% confidence interval is 0.0341. There are 84 homozygotes in gnomad4. There are 1892 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3626 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001397.3 linkuse as main transcript	c.1278+7C>T		splice_region_variant, intron_variant		ENST00000374893.11	NP_001388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE1	ENST00000374893.11 linkuse as main transcript	c.1278+7C>T		splice_region_variant, intron_variant		1	NM_001397.3	ENSP00000364028		P42892-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3625

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.0592

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0241

AC:

6054

AN:

251418

Hom.:

143

AF XY:

0.0244

AC XY:

3321

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.00931

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00826

Gnomad FIN exome

AF:

0.0619

Gnomad NFE exome

AF:

0.0328

Gnomad OTH exome

AF:

0.0256

GnomAD4 exome

AF:

0.0313

AC:

45659

AN:

1460592

Hom.:

882

Cov.:

AF XY:

0.0306

AC XY:

22262

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.00463

Gnomad4 AMR exome

AF:

0.00997

Gnomad4 ASJ exome

AF:

0.0156

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00813

Gnomad4 FIN exome

AF:

0.0605

Gnomad4 NFE exome

AF:

0.0351

Gnomad4 OTH exome

AF:

0.0274

GnomAD4 genome

AF:

0.0238

AC:

3626

AN:

152282

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1892

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.0592

Gnomad4 NFE

AF:

0.0353

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0289

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0311

EpiControl

AF:

0.0303

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.1

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.026

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