2-232480539-C-A

Variant names:

• chr2-232480539-C-A
• rs1190432
• NM_004826.4:c.2152-64G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004826.4(ECEL1):​c.2152-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,597,230 control chromosomes in the GnomAD database, including 38,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2924 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35672 hom.)
• Consequence: ECEL1 NM_004826.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-232480539-C-A is Benign according to our data. Variant chr2-232480539-C-A is described in ClinVar as [Benign]. Clinvar id is 1286601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.2152-64G>T		intron_variant	Intron 16 of 17	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.2146-64G>T		intron_variant	Intron 16 of 17		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.2152-64G>T		intron_variant	Intron 16 of 17	1	NM_004826.4	ENSP00000302051.1
ECEL1	ENST00000409941.1	c.2146-64G>T		intron_variant	Intron 15 of 16	1		ENSP00000386333.1
ECEL1	ENST00000411860.5	c.331-64G>T		intron_variant	Intron 4 of 5	3		ENSP00000412683.1
ECEL1	ENST00000482346.1	n.2463-64G>T		intron_variant	Intron 15 of 16	2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28609 AN: 151962 Hom.: 2927 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.219 AC: 317208 AN: 1445150 Hom.: 35672 Cov.: 30 AF XY: 0.218 AC XY: 156417 AN XY: 718342

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.188 AC: 28624 AN: 152080 Hom.: 2924 Cov.: 33 AF XY: 0.187 AC XY: 13907 AN XY: 74336

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.202

Alfa AF: 0.129 Hom.: 259

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1190432; hg19: chr2-233345249; COSMIC: COSV58813689;