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2-232480281-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004826.4(ECEL1):c.2229-29A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,611,826 control chromosomes in the GnomAD database, including 186,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19080 hom., cov: 32)
Exomes 𝑓: 0.48 ( 167710 hom. )

Consequence

ECEL1
NM_004826.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.522
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 2-232480281-T-G is Benign according to our data. Variant chr2-232480281-T-G is described in ClinVar as [Benign]. Clinvar id is 1255365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ECEL1NM_004826.4 linkuse as main transcriptc.2229-29A>C intron_variant ENST00000304546.6
ECEL1NM_001290787.2 linkuse as main transcriptc.2223-29A>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ECEL1ENST00000304546.6 linkuse as main transcriptc.2229-29A>C intron_variant 1 NM_004826.4 P4O95672-1
ECEL1ENST00000409941.1 linkuse as main transcriptc.2223-29A>C intron_variant 1 A1O95672-2
ECEL1ENST00000411860.5 linkuse as main transcriptc.408-29A>C intron_variant 3
ECEL1ENST00000482346.1 linkuse as main transcriptn.2540-29A>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.498
AC:
75511
AN:
151722
Hom.:
19064
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.521
Gnomad AMI
AF:
0.321
Gnomad AMR
AF:
0.569
Gnomad ASJ
AF:
0.432
Gnomad EAS
AF:
0.685
Gnomad SAS
AF:
0.508
Gnomad FIN
AF:
0.516
Gnomad MID
AF:
0.500
Gnomad NFE
AF:
0.456
Gnomad OTH
AF:
0.475
GnomAD3 exomes
AF:
0.515
AC:
127300
AN:
247124
Hom.:
33299
AF XY:
0.510
AC XY:
68298
AN XY:
133866
show subpopulations
Gnomad AFR exome
AF:
0.530
Gnomad AMR exome
AF:
0.600
Gnomad ASJ exome
AF:
0.444
Gnomad EAS exome
AF:
0.689
Gnomad SAS exome
AF:
0.518
Gnomad FIN exome
AF:
0.518
Gnomad NFE exome
AF:
0.464
Gnomad OTH exome
AF:
0.506
GnomAD4 exome
AF:
0.476
AC:
695619
AN:
1459986
Hom.:
167710
Cov.:
36
AF XY:
0.477
AC XY:
346375
AN XY:
726304
show subpopulations
Gnomad4 AFR exome
AF:
0.521
Gnomad4 AMR exome
AF:
0.596
Gnomad4 ASJ exome
AF:
0.447
Gnomad4 EAS exome
AF:
0.678
Gnomad4 SAS exome
AF:
0.517
Gnomad4 FIN exome
AF:
0.518
Gnomad4 NFE exome
AF:
0.458
Gnomad4 OTH exome
AF:
0.481
GnomAD4 genome
AF:
0.498
AC:
75577
AN:
151840
Hom.:
19080
Cov.:
32
AF XY:
0.502
AC XY:
37268
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.521
Gnomad4 AMR
AF:
0.570
Gnomad4 ASJ
AF:
0.432
Gnomad4 EAS
AF:
0.686
Gnomad4 SAS
AF:
0.508
Gnomad4 FIN
AF:
0.516
Gnomad4 NFE
AF:
0.456
Gnomad4 OTH
AF:
0.476
Alfa
AF:
0.474
Hom.:
3150
Bravo
AF:
0.503
Asia WGS
AF:
0.585
AC:
2033
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Distal arthrogryposis type 5D Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
4.4
Dann
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

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

Other links and lift over

dbSNP: rs2741279; hg19: chr2-233344991; API