rs2741278

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-232480018-G-A
• chr2-232480018-G-C
• chr2-232480018-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004826.4(ECEL1):​c.*135C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 638,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000016 (0 hom.)
• Consequence: ECEL1 NM_004826.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• Publications: 0 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: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>T		3_prime_UTR	Exon 18 of 18	NP_004817.2	A0A6F7YIA8
	ECEL1	NM_001290787.2		c.*135C>T		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>T		3_prime_UTR	Exon 18 of 18	ENSP00000302051.1	O95672-1
	ECEL1	ENST00000862796.1		c.*135C>T		3_prime_UTR	Exon 18 of 18	ENSP00000532855.1
	ECEL1	ENST00000931992.1		c.*135C>T		3_prime_UTR	Exon 18 of 18	ENSP00000602051.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000157 AC: 1 AN: 638554 Hom.: 0 Cov.: 8 AF XY: 0.00000302 AC XY: 1 AN XY: 331636

African (AFR) AF: 0.00 AC: 0 AN: 16050

American (AMR) AF: 0.00 AC: 0 AN: 22590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15156

East Asian (EAS) AF: 0.00 AC: 0 AN: 33108

South Asian (SAS) AF: 0.00 AC: 0 AN: 52546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2364

European-Non Finnish (NFE) AF: 0.00000238 AC: 1 AN: 420710

Other (OTH) AF: 0.00 AC: 0 AN: 31922

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;