chr2-232480539-C-T

Variant names:

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

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>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,597,258 control chromosomes in the GnomAD database, including 90,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7002 hom., cov: 33)
  • Exomes 𝑓: 0.34 (83562 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-T is Benign according to our data. Variant chr2-232480539-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 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>A		intron	N/A	NP_004817.2	A0A6F7YIA8
	ECEL1	NM_001290787.2		c.2146-64G>A		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>A		intron	N/A	ENSP00000302051.1	O95672-1
	ECEL1	ENST00000409941.1	TSL:1	c.2146-64G>A		intron	N/A	ENSP00000386333.1	O95672-2
	ECEL1	ENST00000862796.1		c.2152-64G>A		intron	N/A	ENSP00000532855.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43368 AN: 151962 Hom.: 6987 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.336 AC: 485780 AN: 1445178 Hom.: 83562 Cov.: 30 AF XY: 0.336 AC XY: 241364 AN XY: 718340

African (AFR) AF: 0.129 AC: 4274 AN: 33124

American (AMR) AF: 0.421 AC: 18321 AN: 43536

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7476 AN: 25882

East Asian (EAS) AF: 0.456 AC: 17910 AN: 39284

South Asian (SAS) AF: 0.327 AC: 27930 AN: 85350

European-Finnish (FIN) AF: 0.412 AC: 21670 AN: 52578

Middle Eastern (MID) AF: 0.262 AC: 1285 AN: 4896

European-Non Finnish (NFE) AF: 0.334 AC: 368018 AN: 1100852

Other (OTH) AF: 0.317 AC: 18896 AN: 59676

GnomAD4 genome AF: 0.285 AC: 43411 AN: 152080 Hom.: 7002 Cov.: 33 AF XY: 0.290 AC XY: 21567 AN XY: 74340

African (AFR) AF: 0.139 AC: 5765 AN: 41508

American (AMR) AF: 0.356 AC: 5448 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.440 AC: 2264 AN: 5144

South Asian (SAS) AF: 0.323 AC: 1561 AN: 4826

European-Finnish (FIN) AF: 0.408 AC: 4314 AN: 10584

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22214 AN: 67934

Other (OTH) AF: 0.277 AC: 586 AN: 2112

Alfa AF: 0.194 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	4.4
DANN	Benign	0.75
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;