2-232480539-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• distal arthrogryposis type 5D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004826.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECEL1	NM_004826.4	MANE Select	c.2152-64G>T		intron	N/A	NP_004817.2	A0A6F7YIA8
	ECEL1	NM_001290787.2		c.2146-64G>T		intron	N/A	NP_001277716.1	O95672-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECEL1	ENST00000304546.6	TSL:1 MANE Select	c.2152-64G>T		intron	N/A	ENSP00000302051.1	O95672-1
	ECEL1	ENST00000409941.1	TSL:1	c.2146-64G>T		intron	N/A	ENSP00000386333.1	O95672-2
	ECEL1	ENST00000862796.1		c.2152-64G>T		intron	N/A	ENSP00000532855.1

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

African (AFR) AF: 0.110 AC: 3655 AN: 33122

American (AMR) AF: 0.214 AC: 9311 AN: 43530

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3694 AN: 25876

East Asian (EAS) AF: 0.231 AC: 9085 AN: 39286

South Asian (SAS) AF: 0.175 AC: 14910 AN: 85346

European-Finnish (FIN) AF: 0.196 AC: 10285 AN: 52582

Middle Eastern (MID) AF: 0.169 AC: 827 AN: 4904

European-Non Finnish (NFE) AF: 0.230 AC: 253214 AN: 1100826

Other (OTH) AF: 0.205 AC: 12227 AN: 59678

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

African (AFR) AF: 0.117 AC: 4876 AN: 41510

American (AMR) AF: 0.195 AC: 2977 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1153 AN: 5138

South Asian (SAS) AF: 0.181 AC: 872 AN: 4822

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10586

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15572 AN: 67934

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.129 Hom.: 259

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.82
PhyloP100		-0.24
Mutation Taster		=19/81	disease causing

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

Other links and lift over

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