4-5745189-C-T

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.802-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,518,254 control chromosomes in the GnomAD database, including 280,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 23607 hom., cov: 30)

Exomes 𝑓: 0.62 ( 257232 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.653

Publications

5 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 Gene-Disease associations (from GenCC):

acrofacial dysostosis, Weyers type
Inheritance: AD, Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Ellis-van Creveld syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health

EVC 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=-0.9).

BP6

Variant 4-5745189-C-T is Benign according to our data. Variant chr4-5745189-C-T is described in ClinVar as Benign. ClinVar VariationId is 262782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.802-15C>T		intron_variant	Intron 6 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.802-15C>T		intron_variant	Intron 6 of 20	1	NM_153717.3	ENSP00000264956.6		P57679
EVC	ENST00000509451.1 link	c.802-15C>T		intron_variant	Intron 6 of 11	1		ENSP00000426774.1		E9PCN4

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

83911

AN:

139246

Hom.:

23594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.597

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.597

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.591

GnomAD2 exomes

AF:

0.597

AC:

141222

AN:

236632

AF XY:

0.600

show subpopulations

Gnomad AFR exome

AF:

0.643

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.672

Gnomad EAS exome

AF:

0.348

Gnomad FIN exome

AF:

0.652

Gnomad NFE exome

AF:

0.662

Gnomad OTH exome

AF:

0.625

GnomAD4 exome

AF:

0.623

AC:

859465

AN:

1378912

Hom.:

257232

Cov.:

AF XY:

0.622

AC XY:

426832

AN XY:

686316

show subpopulations

African (AFR)

AF:

0.596

AC:

16171

AN:

27150

American (AMR)

AF:

0.461

AC:

19304

AN:

41882

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

16078

AN:

24626

East Asian (EAS)

AF:

0.337

AC:

13351

AN:

39592

South Asian (SAS)

AF:

0.567

AC:

46101

AN:

81308

European-Finnish (FIN)

AF:

0.627

AC:

31735

AN:

50586

Middle Eastern (MID)

AF:

0.581

AC:

3085

AN:

5312

European-Non Finnish (NFE)

AF:

0.645

AC:

678689

AN:

1051860

Other (OTH)

AF:

0.618

AC:

34951

AN:

56596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

15454

30907

46361

61814

77268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18184

36368

54552

72736

90920

<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:

0.603

AC:

83979

AN:

139342

Hom.:

23607

Cov.:

AF XY:

0.597

AC XY:

40714

AN XY:

68152

show subpopulations

African (AFR)

AF:

0.597

AC:

20487

AN:

34314

American (AMR)

AF:

0.529

AC:

7561

AN:

14300

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2129

AN:

3302

East Asian (EAS)

AF:

0.350

AC:

1800

AN:

5148

South Asian (SAS)

AF:

0.569

AC:

2627

AN:

4616

European-Finnish (FIN)

AF:

0.633

AC:

6276

AN:

9910

Middle Eastern (MID)

AF:

0.607

AC:

165

AN:

272

European-Non Finnish (NFE)

AF:

0.638

AC:

41315

AN:

64708

Other (OTH)

AF:

0.592

AC:

1142

AN:

1930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1895

3790

5684

7579

9474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.00181

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

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 specified

Benign:2

PreventionGenetics, part of Exact Sciences

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;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

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.16

(source)

DANN

Benign

0.37

PhyloP100

-0.65

Mutation Taster

=16/84

disease causing

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over