rs2286343

Positions:

chr4-5745345-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.939+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,612,486 control chromosomes in the GnomAD database, including 96,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9303 hom., cov: 31)

Exomes 𝑓: 0.34 ( 87222 hom. )

Consequence

EVC
NM_153717.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.01367

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.69

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:

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 (BayesDel_noAF=-0.86).

BP6

Variant 4-5745345-C-T is Benign according to our data. Variant chr4-5745345-C-T is described in ClinVar as [Benign]. Clinvar id is 262785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5745345-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3 linkuse as main transcript	c.939+4C>T		splice_donor_region_variant, intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11 linkuse as main transcript	c.939+4C>T		splice_donor_region_variant, intron_variant		1	NM_153717.3	P1
EVC	ENST00000509451.1 linkuse as main transcript	c.939+4C>T		splice_donor_region_variant, intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51696

AN:

150980

Hom.:

9309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.650

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.382

AC:

96022

AN:

251298

Hom.:

19707

AF XY:

0.379

AC XY:

51539

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.649

Gnomad SAS exome

AF:

0.408

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.338

AC:

493256

AN:

1461388

Hom.:

87222

Cov.:

AF XY:

0.340

AC XY:

246919

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.662

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.342

AC:

51725

AN:

151098

Hom.:

9303

Cov.:

AF XY:

0.349

AC XY:

25754

AN XY:

73792

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.651

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.324

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.328

Hom.:

13696

Bravo

AF:

0.348

Asia WGS

AF:

0.508

AC:

1762

AN:

3478

EpiCase

AF:

0.329

EpiControl

AF:

0.331

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 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	Eurofins Ntd Llc (ga)	Mar 02, 2018	- -
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	PreventionGenetics, part of Exact Sciences	-	- -

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	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.3

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.014

dbscSNV1_RF

Benign

0.086

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: -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