rs4688962

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153717.3(EVC):c.1026G>C(p.Leu342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,678 control chromosomes in the GnomAD database, including 186,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L342L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.53 ( 22249 hom., cov: 32)

Exomes 𝑓: 0.47 ( 164530 hom. )

Consequence

EVC
NM_153717.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.359

Variant links:

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]

EVC links:

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]

CRMP1 links:

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=-0.8).

BP6

Variant 4-5748234-G-C is Benign according to our data. Variant chr4-5748234-G-C is described in ClinVar as [Benign]. Clinvar id is 262761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5748234-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.359 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3 linkuse as main transcript	c.1026G>C	p.Leu342=	synonymous_variant	8/21	ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EVC	ENST00000264956.11 linkuse as main transcript	c.1026G>C	p.Leu342=	synonymous_variant	8/21	1	NM_153717.3	P1
EVC	ENST00000509451.1 linkuse as main transcript	c.1026G>C	p.Leu342=	synonymous_variant	8/12	1
CRMP1	ENST00000506216.5 linkuse as main transcript	n.1726C>G		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

79947

AN:

151846

Hom.:

22226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.720

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.510

GnomAD3 exomes

AF:

0.483

AC:

121350

AN:

251364

Hom.:

30336

AF XY:

0.485

AC XY:

65923

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.725

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.625

Gnomad SAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.470

AC:

686654

AN:

1461714

Hom.:

164530

Cov.:

AF XY:

0.473

AC XY:

343664

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.732

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.584

Gnomad4 FIN exome

AF:

0.459

Gnomad4 NFE exome

AF:

0.451

Gnomad4 OTH exome

AF:

0.484

GnomAD4 genome

AF:

0.527

AC:

80026

AN:

151964

Hom.:

22249

Cov.:

AF XY:

0.529

AC XY:

39291

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.720

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.425

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.575

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.514

Alfa

AF:

0.459

Hom.:

5446

Bravo

AF:

0.530

Asia WGS

AF:

0.598

AC:

2080

AN:

3478

EpiCase

AF:

0.438

EpiControl

AF:

0.449

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Ellis-van Creveld syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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

Feb 01, 2024

- -

Curry-Hall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

7.6

Dann

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over