4-5752852-C-T

Position:

chr4-5752852-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.1115C>T(p.Thr372Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,614,038 control chromosomes in the GnomAD database, including 6,743 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 449 hom., cov: 34)

Exomes 𝑓: 0.088 ( 6294 hom. )

Consequence

EVC
NM_153717.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.38

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:

EVC (HGNC:):

EVC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014209151).

BP6

Variant 4-5752852-C-T is Benign according to our data. Variant chr4-5752852-C-T is described in ClinVar as [Benign]. Clinvar id is 262765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5752852-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0907 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.1115C>T	p.Thr372Met	missense_variant	9/21	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.1115C>T	p.Thr372Met	missense_variant	9/21	1	NM_153717.3	ENSP00000264956.6	P57679
EVC	ENST00000509451.1 linkuse as main transcript	c.1115C>T	p.Thr372Met	missense_variant	9/12	1		ENSP00000426774.1	E9PCN4
EVC	ENST00000514919.1 linkuse as main transcript	n.178C>T		non_coding_transcript_exon_variant	1/2	2
CRMP1	ENST00000506216.5 linkuse as main transcript	n.1648-4540G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9600

AN:

152190

Hom.:

450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0352

Gnomad ASJ

AF:

0.0801

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.0521

GnomAD3 exomes

AF:

0.0673

AC:

16901

AN:

251260

Hom.:

779

AF XY:

0.0691

AC XY:

9382

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.0276

Gnomad ASJ exome

AF:

0.0783

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0419

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.0930

Gnomad OTH exome

AF:

0.0694

GnomAD4 exome

AF:

0.0884

AC:

129174

AN:

1461730

Hom.:

6294

Cov.:

AF XY:

0.0872

AC XY:

63411

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.0282

Gnomad4 ASJ exome

AF:

0.0796

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.0992

Gnomad4 OTH exome

AF:

0.0772

GnomAD4 genome

AF:

0.0630

AC:

9601

AN:

152308

Hom.:

449

Cov.:

AF XY:

0.0630

AC XY:

4688

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0801

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0400

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.0926

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0861

Hom.:

772

Bravo

AF:

0.0548

TwinsUK

AF:

0.0992

AC:

368

ALSPAC

AF:

0.107

AC:

412

ESP6500AA

AF:

0.0202

AC:

ESP6500EA

AF:

0.0898

AC:

772

ExAC

AF:

0.0674

AC:

8178

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Benign:3

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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 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	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.76

T;D

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.060

Sift

Benign

0.22

T;T

Sift4G

Benign

0.36

T;D

Polyphen

0.97

D;.

Vest4

0.13

ClinPred

0.016

GERP RS

3.8

Varity_R

0.049

gMVP

0.17

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