2-232480018-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.367

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
ECEL1	NM_004826.4	c.*135C>G		3_prime_UTR_variant	18/18	ENST00000304546.6
ECEL1	NM_001290787.2	c.*135C>G		3_prime_UTR_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECEL1	ENST00000304546.6	c.*135C>G		3_prime_UTR_variant	18/18	1	NM_004826.4	P4
ECEL1	ENST00000411860.5	c.*135C>G		3_prime_UTR_variant	6/6	3
ECEL1	ENST00000482346.1	n.2774C>G		non_coding_transcript_exon_variant	17/17	2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39247 AN: 151992 Hom.: 5698 Cov.: 33

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.: 8 AF XY: 0.303 AC XY: 100302 AN XY: 331228

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.: 33 AF XY: 0.262 AC XY: 19514 AN XY: 74364

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs2741278; hg19: chr2-233344728; COSMIC: COSV58811853; COSMIC: COSV58811853;