2-232480018-G-C

Variant names:

• chr2-232480018-G-C
• rs2741278
• NM_004826.4:c.*135C>G

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.367
• Publications: 7 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=-0.84).
• BP6: Variant 2-232480018-G-C is Benign according to our data. Variant chr2-232480018-G-C is described in ClinVar as Benign. ClinVar VariationId is 1270200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 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.*135C>G		3_prime_UTR	Exon 18 of 18	NP_004817.2	A0A6F7YIA8
	ECEL1	NM_001290787.2		c.*135C>G		3_prime_UTR	Exon 18 of 18	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.*135C>G		3_prime_UTR	Exon 18 of 18	ENSP00000302051.1	O95672-1
	ECEL1	ENST00000862796.1		c.*135C>G		3_prime_UTR	Exon 18 of 18	ENSP00000532855.1
	ECEL1	ENST00000931992.1		c.*135C>G		3_prime_UTR	Exon 18 of 18	ENSP00000602051.1

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

African (AFR) AF: 0.133 AC: 2135 AN: 16044

American (AMR) AF: 0.386 AC: 8699 AN: 22564

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 4308 AN: 15148

East Asian (EAS) AF: 0.460 AC: 15213 AN: 33088

South Asian (SAS) AF: 0.307 AC: 16117 AN: 52516

European-Finnish (FIN) AF: 0.337 AC: 14851 AN: 44038

Middle Eastern (MID) AF: 0.253 AC: 599 AN: 2364

European-Non Finnish (NFE) AF: 0.291 AC: 122086 AN: 420028

Other (OTH) AF: 0.287 AC: 9141 AN: 31880

GnomAD4 genome AF: 0.258 AC: 39291 AN: 152110 Hom.: 5710 Cov.: 33 AF XY: 0.262 AC XY: 19514 AN XY: 74364

African (AFR) AF: 0.135 AC: 5620 AN: 41542

American (AMR) AF: 0.340 AC: 5200 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 935 AN: 3466

East Asian (EAS) AF: 0.436 AC: 2244 AN: 5148

South Asian (SAS) AF: 0.310 AC: 1495 AN: 4816

European-Finnish (FIN) AF: 0.334 AC: 3539 AN: 10586

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19429 AN: 67934

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.149 Hom.: 295

Bravo AF: 0.258

Asia WGS AF: 0.388 AC: 1346 AN: 3478

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	-0.84
CADD	Benign	4.0
DANN	Benign	0.76
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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