Variant rs212522 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001397.3(ECE1):c.1020+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,326 control chromosomes in the GnomAD database, including 13,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 947 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12314 hom. )

Consequence

ECE1
NM_001397.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.60

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=-0.91).

BP6

Variant 1-21255932-C-T is Benign according to our data. Variant chr1-21255932-C-T is described in ClinVar as [Benign]. Clinvar id is 258078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001397.3 linkuse as main transcript	c.1020+15G>A		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.1020+15G>A		intron_variant		1	NM_001397.3	ENSP00000364028		P42892-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15552

AN:

152180

Hom.:

946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0943

Gnomad ASJ

AF:

0.0945

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.0903

GnomAD3 exomes

AF:

0.127

AC:

31899

AN:

250756

Hom.:

2244

AF XY:

0.130

AC XY:

17631

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.0420

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.0902

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.126

AC:

183671

AN:

1461028

Hom.:

12314

Cov.:

AF XY:

0.127

AC XY:

92378

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.0927

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.102

AC:

15582

AN:

152298

Hom.:

947

Cov.:

AF XY:

0.105

AC XY:

7823

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0452

Gnomad4 AMR

AF:

0.0943

Gnomad4 ASJ

AF:

0.0945

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.0922

Alfa

AF:

0.112

Hom.:

1031

Bravo

AF:

0.0917

Asia WGS

AF:

0.158

AC:

551

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.91

CADD

Benign

0.33

DANN

Benign

0.43

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