rs1383180

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1727G>A(p.Arg576Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,613,550 control chromosomes in the GnomAD database, including 99,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. R576L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.32 ( 8380 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90894 hom. )

Consequence

EVC
NM_153717.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.16

Publications

38 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 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 was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0028758347).

BP6

Variant 4-5783715-G-A is Benign according to our data. Variant chr4-5783715-G-A is described in ClinVar as Benign. ClinVar VariationId is 262768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.1727G>A	p.Arg576Gln	missense_variant	Exon 12 of 21	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.1727G>A	p.Arg576Gln	missense_variant	Exon 12 of 21	1	NM_153717.3	ENSP00000264956.6		P57679
CRMP1	ENST00000506216.5 link	n.1648-35403C>T		intron_variant	Intron 12 of 12	5

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48777

AN:

151962

Hom.:

8380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.349

AC:

87463

AN:

250448

AF XY:

0.342

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.349

AC:

509331

AN:

1461470

Hom.:

90894

Cov.:

AF XY:

0.345

AC XY:

250549

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.188

AC:

6276

AN:

33470

American (AMR)

AF:

0.488

AC:

21770

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

10121

AN:

26128

East Asian (EAS)

AF:

0.306

AC:

12153

AN:

39694

South Asian (SAS)

AF:

0.227

AC:

19582

AN:

86234

European-Finnish (FIN)

AF:

0.340

AC:

18181

AN:

53400

Middle Eastern (MID)

AF:

0.341

AC:

1967

AN:

5768

European-Non Finnish (NFE)

AF:

0.358

AC:

398195

AN:

1111758

Other (OTH)

AF:

0.349

AC:

21086

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21436

42871

64307

85742

107178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12528

25056

37584

50112

62640

<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:

0.321

AC:

48781

AN:

152080

Hom.:

8380

Cov.:

AF XY:

0.319

AC XY:

23692

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.203

AC:

8435

AN:

41488

American (AMR)

AF:

0.444

AC:

6795

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1349

AN:

3466

East Asian (EAS)

AF:

0.315

AC:

1628

AN:

5164

South Asian (SAS)

AF:

0.227

AC:

1091

AN:

4814

European-Finnish (FIN)

AF:

0.329

AC:

3481

AN:

10586

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.367

AC:

24962

AN:

67958

Other (OTH)

AF:

0.339

AC:

714

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3416

5123

6831

8539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.354

Hom.:

47524

Bravo

AF:

0.324

TwinsUK

AF:

0.355

AC:

1316

ALSPAC

AF:

0.369

AC:

1423

ESP6500AA

AF:

0.198

AC:

871

ESP6500EA

AF:

0.365

AC:

3135

ExAC

AF:

0.339

AC:

41118

Asia WGS

AF:

0.252

AC:

878

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 03, 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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Ellis-van Creveld syndrome

Benign:3

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 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. -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Curry-Hall syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

PhyloP100

3.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

REVEL

Benign

0.16

Sift

Benign

0.12

Sift4G

Benign

0.085

Polyphen

1.0

Vest4

0.20

ClinPred

0.018

GERP RS

4.1

Varity_R

0.097

gMVP

0.29

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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