chr4-5748190-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_153717.3(EVC):c.982C>T(p.Leu328Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,614,228 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000064 ( 1 hom. )
Consequence
EVC
NM_153717.3 missense
NM_153717.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]
CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.007103622).
BP6
Variant 4-5748190-C-T is Benign according to our data. Variant chr4-5748190-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 349170.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC | NM_153717.3 | c.982C>T | p.Leu328Phe | missense_variant | 8/21 | ENST00000264956.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC | ENST00000264956.11 | c.982C>T | p.Leu328Phe | missense_variant | 8/21 | 1 | NM_153717.3 | P1 | |
EVC | ENST00000509451.1 | c.982C>T | p.Leu328Phe | missense_variant | 8/12 | 1 | |||
CRMP1 | ENST00000506216.5 | n.1770G>A | non_coding_transcript_exon_variant | 13/13 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000227 AC: 57AN: 251488Hom.: 1 AF XY: 0.000206 AC XY: 28AN XY: 135920
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GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461892Hom.: 1 Cov.: 47 AF XY: 0.0000701 AC XY: 51AN XY: 727246
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GnomAD4 genome AF: 0.000151 AC: 23AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74494
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Ellis-van Creveld syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 08, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified in a patient with Jeune asphyxiating thoracic dystrophy in the published literature (McInerney-Leo et al., 2015) who also had a variant in the DNYC2H1 gene and a homozygous variant in the TTC21B gene that was felt to be the cause of the patient's phenotype; This variant is associated with the following publications: (PMID: 28253570, 25492405) - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at