Genetic Variant NM_153717.3:c.2449+15delC (chr4-5802102-AC-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_153717.3(EVC):c.2449+15delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7402 hom., cov: 20)

Exomes 𝑓: 0.34 ( 89767 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.121

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 -16 ACMG points.

BP6

Variant 4-5802102-AC-A is Benign according to our data. Variant chr4-5802102-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 262775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5802102-AC-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.2449+15delC		intron_variant	Intron 16 of 20	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.2449+9delC		intron_variant	Intron 16 of 20	1	NM_153717.3	ENSP00000264956.6		P57679
CRMP1	ENST00000506216.5 link	n.1647+23391delG		intron_variant	Intron 12 of 12	5

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44941

AN:

151864

Hom.:

7392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.362

AC:

90872

AN:

251098

Hom.:

17703

AF XY:

0.373

AC XY:

50664

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.516

Gnomad SAS exome

AF:

0.532

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.344

AC:

502670

AN:

1461582

Hom.:

89767

Cov.:

AF XY:

0.350

AC XY:

254657

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.504

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.296

AC:

44982

AN:

151982

Hom.:

7402

Cov.:

AF XY:

0.305

AC XY:

22648

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.515

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.223

Hom.:

704

Bravo

AF:

0.289

Asia WGS

AF:

0.492

AC:

1708

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Benign:3

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

May 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 07, 2017

GeneDx

Significance: Benign

Review Status: flagged submission

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely 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

Splicing

Name

Calibrated prediction

Score

Prediction

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