rs909431

Positions:

• chr2-232482155-A-G

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.1796+263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,254 control chromosomes in the GnomAD database, including 4,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.23 (4499 hom., cov: 33)
• Consequence: ECEL1 NM_004826.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.55

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=-0.93).
• BP6: Variant 2-232482155-A-G is Benign according to our data. Variant chr2-232482155-A-G is described in ClinVar as [Benign]. Clinvar id is 1238548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.1796+263T>C		intron_variant		ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.1790+263T>C		intron_variant			NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.1796+263T>C		intron_variant		1	NM_004826.4	ENSP00000302051	P4
ECEL1	ENST00000409941.1	c.1790+263T>C		intron_variant		1		ENSP00000386333	A1
ECEL1	ENST00000411860.5	c.41+263T>C		intron_variant		3		ENSP00000412683
ECEL1	ENST00000482346.1	n.2107+263T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34953 AN: 152136 Hom.: 4481 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 35006 AN: 152254 Hom.: 4499 Cov.: 33 AF XY: 0.234 AC XY: 17406 AN XY: 74440

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.202

Alfa AF: 0.235 Hom.: 7267

Bravo AF: 0.229

Asia WGS AF: 0.391 AC: 1357 AN: 3478

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	-0.93
CADD	Benign	0.024
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs909431; hg19: chr2-233346865;