Variant chr2-232480281-T-G 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.2229-29A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,611,826 control chromosomes in the GnomAD database, including 186,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.50 ( 19080 hom., cov: 32)

Exomes 𝑓: 0.48 ( 167710 hom. )

Consequence

ECEL1
NM_004826.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.522

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

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-232480281-T-G is Benign according to our data. Variant chr2-232480281-T-G is described in ClinVar as [Benign]. Clinvar id is 1255365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECEL1	NM_004826.4 linkuse as main transcript	c.2229-29A>C		intron_variant		ENST00000304546.6
ECEL1	NM_001290787.2 linkuse as main transcript	c.2223-29A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ECEL1	ENST00000304546.6 linkuse as main transcript	c.2229-29A>C	intron_variant	1	NM_004826.4	P4	O95672-1
ECEL1	ENST00000409941.1 linkuse as main transcript	c.2223-29A>C	intron_variant	1		A1	O95672-2
ECEL1	ENST00000411860.5 linkuse as main transcript	c.408-29A>C	intron_variant	3
ECEL1	ENST00000482346.1 linkuse as main transcript	n.2540-29A>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75511

AN:

151722

Hom.:

19064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.475

GnomAD3 exomes

AF:

0.515

AC:

127300

AN:

247124

Hom.:

33299

AF XY:

0.510

AC XY:

68298

AN XY:

133866

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.464

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.476

AC:

695619

AN:

1459986

Hom.:

167710

Cov.:

AF XY:

0.477

AC XY:

346375

AN XY:

726304

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.596

Gnomad4 ASJ exome

AF:

0.447

Gnomad4 EAS exome

AF:

0.678

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.481

GnomAD4 genome

AF:

0.498

AC:

75577

AN:

151840

Hom.:

19080

Cov.:

AF XY:

0.502

AC XY:

37268

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.521

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.686

Gnomad4 SAS

AF:

0.508

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.456

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.474

Hom.:

3150

Bravo

AF:

0.503

Asia WGS

AF:

0.585

AC:

2033

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

Distal arthrogryposis type 5D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

DANN

Benign

0.73

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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