rs6750085

chr2-232483209-C-G

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.1507-30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,583,368 control chromosomes in the GnomAD database, including 134,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10580 hom., cov: 33)
  • Exomes 𝑓: 0.41 (123454 hom.)
• Consequence: ECEL1 NM_004826.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.391

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=-0.84).
• BP6: Variant 2-232483209-C-G is Benign according to our data. Variant chr2-232483209-C-G is described in ClinVar as [Benign]. Clinvar id is 1250015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECEL1	NM_004826.4	c.1507-30G>C		intron_variant		ENST00000304546.6
ECEL1	NM_001290787.2	c.1507-30G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECEL1	ENST00000304546.6	c.1507-30G>C		intron_variant		1	NM_004826.4	P4
ECEL1	ENST00000409941.1	c.1507-30G>C		intron_variant		1		A1
ECEL1	ENST00000482346.1	n.1818-30G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54671 AN: 151958 Hom.: 10584 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.405

GnomAD3 exomes AF: 0.393 AC: 78109 AN: 199000 Hom.: 15715 AF XY: 0.397 AC XY: 42356 AN XY: 106798

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.350

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.412 AC: 589493 AN: 1431296 Hom.: 123454 Cov.: 40 AF XY: 0.411 AC XY: 291447 AN XY: 709178

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.359 AC: 54663 AN: 152072 Hom.: 10580 Cov.: 33 AF XY: 0.360 AC XY: 26777 AN XY: 74318

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.402

Alfa AF: 0.406 Hom.: 2384

Bravo AF: 0.350

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Distal arthrogryposis type 5D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.59

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: rs6750085; hg19: chr2-233347919; COSMIC: COSV58811117; COSMIC: COSV58811117;