rs1031919

Positions:

chr4-5801942-T-C

Variant summary

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

The NM_153717.3(EVC):c.2305-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,612,074 control chromosomes in the GnomAD database, including 432,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39628 hom., cov: 33)

Exomes 𝑓: 0.73 ( 392389 hom. )

Consequence

EVC
NM_153717.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005523

Clinical Significance

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

Conservation

PhyloP100: -1.05

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=-0.9).

BP6

Variant 4-5801942-T-C is Benign according to our data. Variant chr4-5801942-T-C is described in ClinVar as [Benign]. Clinvar id is 262774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5801942-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 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.2305-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 linkuse as main transcript	c.2305-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_153717.3	ENSP00000264956	P1
CRMP1	ENST00000506216.5 linkuse as main transcript	n.1647+23552A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.721

AC:

109631

AN:

152034

Hom.:

39592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.844

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.812

Gnomad FIN

AF:

0.788

Gnomad MID

AF:

0.675

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.704

GnomAD3 exomes

AF:

0.719

AC:

179567

AN:

249798

Hom.:

65108

AF XY:

0.727

AC XY:

98183

AN XY:

135070

show subpopulations

Gnomad AFR exome

AF:

0.716

Gnomad AMR exome

AF:

0.644

Gnomad ASJ exome

AF:

0.685

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.820

Gnomad FIN exome

AF:

0.783

Gnomad NFE exome

AF:

0.733

Gnomad OTH exome

AF:

0.715

GnomAD4 exome

AF:

0.732

AC:

1068320

AN:

1459922

Hom.:

392389

Cov.:

AF XY:

0.734

AC XY:

533351

AN XY:

726242

show subpopulations

Gnomad4 AFR exome

AF:

0.708

Gnomad4 AMR exome

AF:

0.650

Gnomad4 ASJ exome

AF:

0.682

Gnomad4 EAS exome

AF:

0.537

Gnomad4 SAS exome

AF:

0.819

Gnomad4 FIN exome

AF:

0.776

Gnomad4 NFE exome

AF:

0.736

Gnomad4 OTH exome

AF:

0.715

GnomAD4 genome

AF:

0.721

AC:

109717

AN:

152152

Hom.:

39628

Cov.:

AF XY:

0.724

AC XY:

53850

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.685

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.552

Gnomad4 SAS

AF:

0.811

Gnomad4 FIN

AF:

0.788

Gnomad4 NFE

AF:

0.734

Gnomad4 OTH

AF:

0.698

Alfa

AF:

0.728

Hom.:

17451

Bravo

AF:

0.708

Asia WGS

AF:

0.678

AC:

2358

AN:

3478

EpiCase

AF:

0.718

EpiControl

AF:

0.722

ClinVar

Significance: Benign

Submissions summary: Benign:10

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, 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 12, 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

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.93

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000055

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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