4-5748276-A-G

Position:

chr4-5748276-A-G

Variant summary

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

The NM_153717.3(EVC):c.1068A>G(p.Leu356Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,844 control chromosomes in the GnomAD database, including 83,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6401 hom., cov: 32)

Exomes 𝑓: 0.32 ( 77331 hom. )

Consequence

EVC
NM_153717.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.912

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:):

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=-0.89).

BP6

Variant 4-5748276-A-G is Benign according to our data. Variant chr4-5748276-A-G is described in ClinVar as [Benign]. Clinvar id is 262762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5748276-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.912 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC	NM_153717.3 linkuse as main transcript	c.1068A>G	p.Leu356Leu	synonymous_variant	8/21	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EVC	ENST00000264956.11 linkuse as main transcript	c.1068A>G	p.Leu356Leu	synonymous_variant	8/21	1	NM_153717.3	ENSP00000264956.6	P57679
EVC	ENST00000509451.1 linkuse as main transcript	c.1068A>G	p.Leu356Leu	synonymous_variant	8/12	1		ENSP00000426774.1	E9PCN4
CRMP1	ENST00000506216.5 linkuse as main transcript	n.1684T>C		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40538

AN:

151974

Hom.:

6406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.298

AC:

74813

AN:

251348

Hom.:

12019

AF XY:

0.296

AC XY:

40148

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.350

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.319

AC:

466536

AN:

1461752

Hom.:

77331

Cov.:

AF XY:

0.316

AC XY:

229622

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0932

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.340

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.267

AC:

40547

AN:

152092

Hom.:

6401

Cov.:

AF XY:

0.263

AC XY:

19533

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.322

Hom.:

5851

Bravo

AF:

0.264

Asia WGS

AF:

0.176

AC:

615

AN:

3478

EpiCase

AF:

0.354

EpiControl

AF:

0.344

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Benign:4

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. -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:2

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	-	- -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.89

CADD

Benign

2.1

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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