rs2302075

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.1346C>A(p.Thr449Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,613,976 control chromosomes in the GnomAD database, including 518,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 53273 hom., cov: 32)

Exomes 𝑓: 0.80 ( 464770 hom. )

Consequence

EVC
NM_153717.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.433

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=5.731524E-7).

BP6

Variant 4-5753815-C-A is Benign according to our data. Variant chr4-5753815-C-A is described in ClinVar as [Benign]. Clinvar id is 167044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5753815-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 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.1346C>A	p.Thr449Lys	missense_variant	10/21	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.1346C>A	p.Thr449Lys	missense_variant	10/21	1	NM_153717.3	ENSP00000264956.6	P57679
EVC	ENST00000509451.1 linkuse as main transcript	c.1346C>A	p.Thr449Lys	missense_variant	10/12	1		ENSP00000426774.1	E9PCN4
EVC	ENST00000514919.1 linkuse as main transcript	n.409C>A		non_coding_transcript_exon_variant	2/2	2
CRMP1	ENST00000506216.5 linkuse as main transcript	n.1648-5503G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126668

AN:

152046

Hom.:

53221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.785

Gnomad AMR

AF:

0.771

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.772

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.788

Gnomad OTH

AF:

0.822

GnomAD3 exomes

AF:

0.791

AC:

198863

AN:

251462

Hom.:

79004

AF XY:

0.789

AC XY:

107203

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.961

Gnomad AMR exome

AF:

0.713

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.812

Gnomad SAS exome

AF:

0.779

Gnomad FIN exome

AF:

0.768

Gnomad NFE exome

AF:

0.791

Gnomad OTH exome

AF:

0.784

GnomAD4 exome

AF:

0.797

AC:

1164596

AN:

1461812

Hom.:

464770

Cov.:

AF XY:

0.795

AC XY:

578466

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.961

Gnomad4 AMR exome

AF:

0.720

Gnomad4 ASJ exome

AF:

0.831

Gnomad4 EAS exome

AF:

0.814

Gnomad4 SAS exome

AF:

0.781

Gnomad4 FIN exome

AF:

0.763

Gnomad4 NFE exome

AF:

0.796

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.833

AC:

126777

AN:

152164

Hom.:

53273

Cov.:

AF XY:

0.829

AC XY:

61676

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.956

Gnomad4 AMR

AF:

0.770

Gnomad4 ASJ

AF:

0.832

Gnomad4 EAS

AF:

0.819

Gnomad4 SAS

AF:

0.778

Gnomad4 FIN

AF:

0.772

Gnomad4 NFE

AF:

0.788

Gnomad4 OTH

AF:

0.824

Alfa

AF:

0.796

Hom.:

109652

Bravo

AF:

0.839

TwinsUK

AF:

0.809

AC:

2999

ALSPAC

AF:

0.809

AC:

3119

ESP6500AA

AF:

0.954

AC:

4203

ESP6500EA

AF:

0.801

AC:

6886

ExAC

AF:

0.796

AC:

96695

Asia WGS

AF:

0.789

AC:

2746

AN:

3478

EpiCase

AF:

0.794

EpiControl

AF:

0.795

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 03, 2014	- -
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, 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+	-	- -

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	- -

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

0.047

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.44

DANN

Benign

0.81

DEOGEN2

Benign

0.062

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.038

T;T

MetaRNN

Benign

5.7e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.8

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

1.9

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.062

ClinPred

0.0016

GERP RS

-0.27

Varity_R

0.035

gMVP

0.047

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