4-5810468-A-G

Position:

chr4-5810468-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.2894+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,588,286 control chromosomes in the GnomAD database, including 422,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39504 hom., cov: 33)

Exomes 𝑓: 0.73 ( 382621 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0510

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 (BayesDel_noAF=-0.94).

BP6

Variant 4-5810468-A-G is Benign according to our data. Variant chr4-5810468-A-G is described in ClinVar as [Benign]. Clinvar id is 262778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5810468-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.2894+18A>G		intron_variant		ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.2894+18A>G		intron_variant		1	NM_153717.3	ENSP00000264956.6		P57679
CRMP1	ENST00000506216.5 link	n.1647+15026T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109313

AN:

151960

Hom.:

39471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.846

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.777

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.698

GnomAD3 exomes

AF:

0.720

AC:

156622

AN:

217576

Hom.:

56740

AF XY:

0.729

AC XY:

85288

AN XY:

116934

show subpopulations

Gnomad AFR exome

AF:

0.720

Gnomad AMR exome

AF:

0.639

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.560

Gnomad SAS exome

AF:

0.839

Gnomad FIN exome

AF:

0.770

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.714

GnomAD4 exome

AF:

0.729

AC:

1046455

AN:

1436208

Hom.:

382621

Cov.:

AF XY:

0.732

AC XY:

521588

AN XY:

712766

show subpopulations

Gnomad4 AFR exome

AF:

0.718

Gnomad4 AMR exome

AF:

0.644

Gnomad4 ASJ exome

AF:

0.687

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.835

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.713

GnomAD4 genome

AF:

0.719

AC:

109400

AN:

152078

Hom.:

39504

Cov.:

AF XY:

0.722

AC XY:

53680

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.680

Gnomad4 ASJ

AF:

0.684

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.777

Gnomad4 NFE

AF:

0.731

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.713

Hom.:

39682

Bravo

AF:

0.705

Asia WGS

AF:

0.708

AC:

2466

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

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

- -

Ellis-van Creveld syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.8

DANN

Benign

0.42

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