Variant rs12562197 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.1164-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,612,490 control chromosomes in the GnomAD database, including 57,766 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 0.21 ( 4204 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53562 hom. )

Consequence

ECE1
NM_001397.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001958

Clinical Significance

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

Conservation

PhyloP100: -0.00100

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=-0.81).

BP6

Variant 1-21245108-G-A is Benign according to our data. Variant chr1-21245108-G-A is described in ClinVar as [Benign]. Clinvar id is 258081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 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.1164-5C>T		splice_region_variant, splice_polypyrimidine_tract_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.1164-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001397.3	ENSP00000364028		P42892-1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32097

AN:

152026

Hom.:

4207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.236

AC:

59041

AN:

250150

Hom.:

7594

AF XY:

0.240

AC XY:

32449

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.0615

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.266

AC:

387964

AN:

1460346

Hom.:

53562

Cov.:

AF XY:

0.264

AC XY:

191880

AN XY:

726528

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.211

AC:

32100

AN:

152144

Hom.:

4204

Cov.:

AF XY:

0.209

AC XY:

15582

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0637

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.263

Hom.:

12850

Bravo

AF:

0.199

Asia WGS

AF:

0.154

AC:

539

AN:

3478

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

-0.81

CADD

Benign

4.7

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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