Variant chr1-21227230-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001397.3(ECE1):c.1782-4C>A 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 0.0325 in 1,613,586 control chromosomes in the GnomAD database, including 1,009 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 0.027 ( 86 hom., cov: 32)

Exomes 𝑓: 0.033 ( 923 hom. )

Consequence

ECE1
NM_001397.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.003547

Clinical Significance

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

Conservation

PhyloP100: -0.370

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-21227230-G-T is Benign according to our data. Variant chr1-21227230-G-T is described in ClinVar as [Benign]. Clinvar id is 258087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0275 (4184/152316) while in subpopulation NFE AF= 0.0343 (2334/68026). AF 95% confidence interval is 0.0331. There are 86 homozygotes in gnomad4. There are 2116 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE1	NM_001397.3 linkuse as main transcript	c.1782-4C>A		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.1782-4C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001397.3	ENSP00000364028		P42892-1

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4184

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0281

AC:

7068

AN:

251478

Hom.:

130

AF XY:

0.0282

AC XY:

3828

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0361

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0129

Gnomad FIN exome

AF:

0.0667

Gnomad NFE exome

AF:

0.0358

Gnomad OTH exome

AF:

0.0270

GnomAD4 exome

AF:

0.0330

AC:

48250

AN:

1461270

Hom.:

923

Cov.:

AF XY:

0.0326

AC XY:

23685

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0378

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0135

Gnomad4 FIN exome

AF:

0.0631

Gnomad4 NFE exome

AF:

0.0357

Gnomad4 OTH exome

AF:

0.0315

GnomAD4 genome

AF:

0.0275

AC:

4184

AN:

152316

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

2116

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0427

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0660

Gnomad4 NFE

AF:

0.0343

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0311

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0342

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

-0.36

CADD

Benign

9.9

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0035

dbscSNV1_RF

Benign

0.040

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