4-5810468-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 262778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	NM_153717.3	MANE Select	c.2894+18A>G		intron	N/A	NP_714928.1
	EVC	NM_001306090.2		c.2894+18A>G		intron	N/A	NP_001293019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.2894+18A>G		intron	N/A	ENSP00000264956.6
	CRMP1	ENST00000506216.5	TSL:5	n.1647+15026T>C		intron	N/A

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

GnomAD2 exomes

AF:

0.720

AC:

156622

AN:

217576

AF XY:

0.729

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 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

African (AFR)

AF:

0.718

AC:

23802

AN:

33150

American (AMR)

AF:

0.644

AC:

26488

AN:

41128

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

17575

AN:

25596

East Asian (EAS)

AF:

0.548

AC:

21449

AN:

39122

South Asian (SAS)

AF:

0.835

AC:

69118

AN:

82764

European-Finnish (FIN)

AF:

0.766

AC:

39984

AN:

52200

Middle Eastern (MID)

AF:

0.689

AC:

3892

AN:

5648

European-Non Finnish (NFE)

AF:

0.731

AC:

801753

AN:

1097142

Other (OTH)

AF:

0.713

AC:

42394

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

13926

27852

41778

55704

69630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19840

39680

59520

79360

99200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.719

AC:

109400

AN:

152078

Hom.:

39504

Cov.:

AF XY:

0.722

AC XY:

53680

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.709

AC:

29434

AN:

41490

American (AMR)

AF:

0.680

AC:

10386

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

2373

AN:

3468

East Asian (EAS)

AF:

0.562

AC:

2891

AN:

5142

South Asian (SAS)

AF:

0.831

AC:

4000

AN:

4814

European-Finnish (FIN)

AF:

0.777

AC:

8224

AN:

10582

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.731

AC:

49670

AN:

67992

Other (OTH)

AF:

0.694

AC:

1462

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1647

3295

4942

6590

8237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.712

Hom.:

51336

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

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.

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

Ellis-van Creveld syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.8

(source)

DANN

Benign

0.42

PhyloP100

-0.051

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over