rs1383180

Positions:

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Benign (★★).

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

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 -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 id is 262768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5783715-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.1727G>A	p.Arg576Gln	missense_variant	12/21	ENST00000264956.11	NP_714928.1	P57679

Ensembl

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

GnomAD3 exomes

AF:

0.349

AC:

87463

AN:

250448

Hom.:

16091

AF XY:

0.342

AC XY:

46258

AN XY:

135398

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 SAS exome

AF:

0.222

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

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.321

AC:

48781

AN:

152080

Hom.:

8380

Cov.:

AF XY:

0.319

AC XY:

23692

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.339

Alfa

AF:

0.360

Hom.:

24610

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

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

Ellis-van Creveld syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 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 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. -

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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

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

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

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