rs899691

Variant names:

Variant summary

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

The NM_153717.3(EVC):c.1099-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,612,372 control chromosomes in the GnomAD database, including 148,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11572 hom., cov: 33)

Exomes 𝑓: 0.43 ( 136447 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.802

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=-0.88).

BP6

Variant 4-5752817-T-C is Benign according to our data. Variant chr4-5752817-T-C is described in ClinVar as [Benign]. Clinvar id is 262764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5752817-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.1099-19T>C		intron_variant	Intron 8 of 20	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVC	ENST00000264956.11 link	c.1099-19T>C	intron_variant	Intron 8 of 20	1	NM_153717.3	ENSP00000264956.6	P57679
EVC	ENST00000509451.1 link	c.1099-19T>C	intron_variant	Intron 8 of 11	1		ENSP00000426774.1	E9PCN4
EVC	ENST00000514919.1 link	n.143T>C	non_coding_transcript_exon_variant	Exon 1 of 2	2
CRMP1	ENST00000506216.5 link	n.1648-4505A>G	intron_variant	Intron 12 of 12	5

Frequencies

GnomAD3 genomes

AF:

0.373

AC:

56686

AN:

152032

Hom.:

11576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.376

GnomAD3 exomes

AF:

0.408

AC:

102352

AN:

250600

Hom.:

21919

AF XY:

0.404

AC XY:

54848

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.427

AC:

623859

AN:

1460222

Hom.:

136447

Cov.:

AF XY:

0.423

AC XY:

307433

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.373

AC:

56699

AN:

152150

Hom.:

11572

Cov.:

AF XY:

0.369

AC XY:

27474

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.439

Hom.:

16228

Bravo

AF:

0.369

Asia WGS

AF:

0.273

AC:

950

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 08, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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:2

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Curry-Hall syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

DANN

Benign

0.60

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