Variant 2-232480018-G-C 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_004826.4(ECEL1):c.*135C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 789,780 control chromosomes in the GnomAD database, including 36,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5710 hom., cov: 33)

Exomes 𝑓: 0.30 ( 30477 hom. )

Consequence

ECEL1
NM_004826.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.367

Variant links:

Genes affected

ECEL1 (HGNC:3147): (endothelin converting enzyme like 1) This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ECEL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-232480018-G-C is Benign according to our data. Variant chr2-232480018-G-C is described in ClinVar as [Benign]. Clinvar id is 1270200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECEL1	NM_004826.4 linkuse as main transcript	c.*135C>G		3_prime_UTR_variant	18/18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2 linkuse as main transcript	c.*135C>G		3_prime_UTR_variant	18/18		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6 linkuse as main transcript	c.*135C>G	3_prime_UTR_variant	18/18	1	NM_004826.4	ENSP00000302051	P4	O95672-1
ECEL1	ENST00000411860.5 linkuse as main transcript	c.*135C>G	3_prime_UTR_variant	6/6	3		ENSP00000412683
ECEL1	ENST00000482346.1 linkuse as main transcript	n.2774C>G	non_coding_transcript_exon_variant	17/17	2

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39247

AN:

151992

Hom.:

5698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.303

AC:

193149

AN:

637670

Hom.:

30477

Cov.:

AF XY:

0.303

AC XY:

100302

AN XY:

331228

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.291

Gnomad4 OTH exome

AF:

0.287

GnomAD4 genome

AF:

0.258

AC:

39291

AN:

152110

Hom.:

5710

Cov.:

AF XY:

0.262

AC XY:

19514

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.436

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.149

Hom.:

295

Bravo

AF:

0.258

Asia WGS

AF:

0.388

AC:

1346

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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