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GeneBe

2-232480452-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP3BP6_ModerateBS1

The NM_004826.4(ECEL1):c.2175G>A(p.Ser725=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,613,864 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00087 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

ECEL1
NM_004826.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.62
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-232480452-C-T is Benign according to our data. Variant chr2-232480452-C-T is described in ClinVar as [Benign]. Clinvar id is 778049.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000873 (133/152310) while in subpopulation AFR AF= 0.00269 (112/41566). AF 95% confidence interval is 0.00229. There are 1 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ECEL1NM_004826.4 linkuse as main transcriptc.2175G>A p.Ser725= synonymous_variant 17/18 ENST00000304546.6
ECEL1NM_001290787.2 linkuse as main transcriptc.2169G>A p.Ser723= synonymous_variant 17/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ECEL1ENST00000304546.6 linkuse as main transcriptc.2175G>A p.Ser725= synonymous_variant 17/181 NM_004826.4 P4O95672-1
ECEL1ENST00000409941.1 linkuse as main transcriptc.2169G>A p.Ser723= synonymous_variant 16/171 A1O95672-2
ECEL1ENST00000411860.5 linkuse as main transcriptc.354G>A p.Ser118= synonymous_variant 5/63
ECEL1ENST00000482346.1 linkuse as main transcriptn.2486G>A non_coding_transcript_exon_variant 16/172

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000861
AC:
131
AN:
152192
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000207
AC:
52
AN:
250986
Hom.:
1
AF XY:
0.000162
AC XY:
22
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00240
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.000816
GnomAD4 exome
AF:
0.0000951
AC:
139
AN:
1461554
Hom.:
0
Cov.:
35
AF XY:
0.000100
AC XY:
73
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.00224
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000873
AC:
133
AN:
152310
Hom.:
1
Cov.:
33
AF XY:
0.000967
AC XY:
72
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00269
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000704
Hom.:
0
Bravo
AF:
0.00103
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
17
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.51
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.51
Position offset: -19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199696717; hg19: chr2-233345162; COSMIC: COSV58813123; API