2-232480539-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004826.4(ECEL1):​c.2152-64G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ECEL1 NM_004826.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.2152-64G>C		intron_variant	Intron 16 of 17	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.2146-64G>C		intron_variant	Intron 16 of 17		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.2152-64G>C		intron_variant	Intron 16 of 17	1	NM_004826.4	ENSP00000302051.1
ECEL1	ENST00000409941.1	c.2146-64G>C		intron_variant	Intron 15 of 16	1		ENSP00000386333.1
ECEL1	ENST00000411860.5	c.331-64G>C		intron_variant	Intron 4 of 5	3		ENSP00000412683.1
ECEL1	ENST00000482346.1	n.2463-64G>C		intron_variant	Intron 15 of 16	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445956 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718750

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.79

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: rs1190432; hg19: chr2-233345249;