rs2229450
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The ENST00000374893.11(ECE1):c.1155C>T(p.Thr385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,613,978 control chromosomes in the GnomAD database, including 51,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.20 ( 3674 hom., cov: 32)
Exomes 𝑓: 0.25 ( 47655 hom. )
Consequence
ECE1
ENST00000374893.11 synonymous
ENST00000374893.11 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.05
Genes affected
ECE1 (HGNC:3146): (endothelin converting enzyme 1) The protein encoded by this gene is involved in proteolytic processing of endothelin precursors to biologically active peptides. Mutations in this gene are associated with Hirschsprung disease, cardiac defects and autonomic dysfunction. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Sep 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 1-21247229-G-A is Benign according to our data. Variant chr1-21247229-G-A is described in ClinVar as [Benign]. Clinvar id is 258080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-6.05 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ECE1 | NM_001397.3 | c.1155C>T | p.Thr385= | synonymous_variant | 9/19 | ENST00000374893.11 | NP_001388.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ECE1 | ENST00000374893.11 | c.1155C>T | p.Thr385= | synonymous_variant | 9/19 | 1 | NM_001397.3 | ENSP00000364028 |
Frequencies
GnomAD3 genomes AF: 0.196 AC: 29880AN: 152084Hom.: 3676 Cov.: 32
GnomAD3 genomes
AF:
AC:
29880
AN:
152084
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.222 AC: 55757AN: 251464Hom.: 6823 AF XY: 0.224 AC XY: 30465AN XY: 135908
GnomAD3 exomes
AF:
AC:
55757
AN:
251464
Hom.:
AF XY:
AC XY:
30465
AN XY:
135908
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.250 AC: 365674AN: 1461778Hom.: 47655 Cov.: 37 AF XY: 0.248 AC XY: 180415AN XY: 727180
GnomAD4 exome
AF:
AC:
365674
AN:
1461778
Hom.:
Cov.:
37
AF XY:
AC XY:
180415
AN XY:
727180
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.196 AC: 29879AN: 152200Hom.: 3674 Cov.: 32 AF XY: 0.193 AC XY: 14375AN XY: 74398
GnomAD4 genome
AF:
AC:
29879
AN:
152200
Hom.:
Cov.:
32
AF XY:
AC XY:
14375
AN XY:
74398
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
476
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at