4-5729347-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.341C>T(p.Ala114Val) variant causes a missense change. The variant allele was found at a frequency of 0.0146 in 1,614,036 control chromosomes in the GnomAD database, including 1,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A114S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.056 ( 737 hom., cov: 32)

Exomes 𝑓: 0.010 ( 719 hom. )

Consequence

EVC
NM_153717.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.46

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

acrofacial dysostosis, Weyers type
Inheritance: AD, Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Ellis-van Creveld syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health

EVC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024841726).

BP6

Variant 4-5729347-C-T is Benign according to our data. Variant chr4-5729347-C-T is described in ClinVar as Benign. ClinVar VariationId is 262779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.341C>T	p.Ala114Val	missense_variant	Exon 3 of 21	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.341C>T	p.Ala114Val	missense_variant	Exon 3 of 21	1	NM_153717.3	ENSP00000264956.6
EVC	ENST00000509451.1 link	c.341C>T	p.Ala114Val	missense_variant	Exon 3 of 12	1		ENSP00000426774.1

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

8478

AN:

152040

Hom.:

734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0313

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00450

Gnomad OTH

AF:

0.0454

GnomAD2 exomes

AF:

0.0197

AC:

4949

AN:

251488

AF XY:

0.0179

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00489

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0103

AC:

15090

AN:

1461878

Hom.:

719

Cov.:

AF XY:

0.0104

AC XY:

7555

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.190

AC:

6350

AN:

33478

American (AMR)

AF:

0.0120

AC:

536

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

292

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0284

AC:

2453

AN:

86258

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0269

AC:

155

AN:

5768

European-Non Finnish (NFE)

AF:

0.00380

AC:

4222

AN:

1112000

Other (OTH)

AF:

0.0174

AC:

1050

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

842

1684

2527

3369

4211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0559

AC:

8504

AN:

152158

Hom.:

737

Cov.:

AF XY:

0.0549

AC XY:

4084

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.181

AC:

7501

AN:

41460

American (AMR)

AF:

0.0216

AC:

330

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0313

AC:

151

AN:

4822

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00450

AC:

306

AN:

68014

Other (OTH)

AF:

0.0449

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

358

715

1073

1430

1788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0217

Hom.:

952

Bravo

AF:

0.0627

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.177

AC:

778

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.0236

AC:

2866

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00587

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Benign:3

Jun 15, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 27, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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;C0457013:Curry-Hall syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PhyloP100

4.5

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.39

ClinPred

0.036

GERP RS

4.9

Varity_R

0.61

gMVP

0.52

Mutation Taster

=85/15

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over