2-232480539-C-T

Position:

• chr2-232480539-C-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>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

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-T is Benign according to our data. Variant chr2-232480539-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECEL1	NM_004826.4	c.2152-64G>A		intron_variant		ENST00000304546.6
ECEL1	NM_001290787.2	c.2146-64G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECEL1	ENST00000304546.6	c.2152-64G>A		intron_variant		1	NM_004826.4	P4
ECEL1	ENST00000409941.1	c.2146-64G>A		intron_variant		1		A1
ECEL1	ENST00000411860.5	c.331-64G>A		intron_variant		3
ECEL1	ENST00000482346.1	n.2463-64G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.317

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.277

Alfa AF: 0.194 Hom.: 259

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs1190432; hg19: chr2-233345249;