rs115976359
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_153717.3(EVC):c.2505G>A(p.Ser835=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,614,136 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 19 hom., cov: 32)
Exomes 𝑓: 0.013 ( 233 hom. )
Consequence
EVC
NM_153717.3 synonymous
NM_153717.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.83
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 4-5804785-G-A is Benign according to our data. Variant chr4-5804785-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.83 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0107 (1634/152258) while in subpopulation SAS AF= 0.0424 (204/4814). AF 95% confidence interval is 0.0376. There are 19 homozygotes in gnomad4. There are 874 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 19 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC | NM_153717.3 | c.2505G>A | p.Ser835= | synonymous_variant | 17/21 | ENST00000264956.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC | ENST00000264956.11 | c.2505G>A | p.Ser835= | synonymous_variant | 17/21 | 1 | NM_153717.3 | P1 | |
CRMP1 | ENST00000506216.5 | n.1647+20709C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0107 AC: 1634AN: 152140Hom.: 19 Cov.: 32
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GnomAD3 exomes AF: 0.0148 AC: 3722AN: 251468Hom.: 59 AF XY: 0.0168 AC XY: 2289AN XY: 135914
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GnomAD4 exome AF: 0.0134 AC: 19594AN: 1461878Hom.: 233 Cov.: 32 AF XY: 0.0145 AC XY: 10544AN XY: 727240
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 07, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Ellis-van Creveld syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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