Variant 2-232480086-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_004826.4(ECEL1):c.*67A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,510,460 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

ECEL1
NM_004826.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.449

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 2-232480086-T-A is Benign according to our data. Variant chr2-232480086-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208946.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1610/152196) while in subpopulation AFR AF= 0.0366 (1521/41546). AF 95% confidence interval is 0.0351. There are 37 homozygotes in gnomad4. There are 750 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECEL1	NM_004826.4 linkuse as main transcript	c.*67A>T		3_prime_UTR_variant	18/18	ENST00000304546.6
ECEL1	NM_001290787.2 linkuse as main transcript	c.*67A>T		3_prime_UTR_variant	18/18

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECEL1	ENST00000304546.6 linkuse as main transcript	c.*67A>T	3_prime_UTR_variant	18/18	1	NM_004826.4	P4	O95672-1
ECEL1	ENST00000411860.5 linkuse as main transcript	c.*67A>T	3_prime_UTR_variant	6/6	3
ECEL1	ENST00000482346.1 linkuse as main transcript	n.2706A>T	non_coding_transcript_exon_variant	17/17	2

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1608

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00718

GnomAD4 exome

AF:

0.00130

AC:

1760

AN:

1358264

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

784

AN XY:

678092

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.000977

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.0106

AC:

1610

AN:

152196

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

750

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00807

Hom.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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