rs41269555

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_153717.3(EVC):c.780G>A(p.Lys260Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 1,519,022 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 86 hom. )

Consequence

EVC
NM_153717.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.525

Publications

2 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 4-5741793-G-A is Benign according to our data. Variant chr4-5741793-G-A is described in ClinVar as Benign. ClinVar VariationId is 198283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.525 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AD,Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 6 of 21	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 6 of 21	1	NM_153717.3	ENSP00000264956.6		P57679
EVC	ENST00000509451.1 link	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 6 of 12	1		ENSP00000426774.1		E9PCN4

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

996

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00925

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00777

AC:

1940

AN:

249674

AF XY:

0.00772

show subpopulations

Gnomad AFR exome

AF:

0.00170

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00660

GnomAD4 exome

AF:

0.00885

AC:

12102

AN:

1366818

Hom.:

Cov.:

AF XY:

0.00860

AC XY:

5890

AN XY:

685054

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

31820

American (AMR)

AF:

0.00180

AC:

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.00263

AC:

AN:

25462

East Asian (EAS)

AF:

0.00

AC:

AN:

39010

South Asian (SAS)

AF:

0.0000239

AC:

AN:

83748

European-Finnish (FIN)

AF:

0.00903

AC:

480

AN:

53144

Middle Eastern (MID)

AF:

0.000400

AC:

AN:

5006

European-Non Finnish (NFE)

AF:

0.0107

AC:

11042

AN:

1027342

Other (OTH)

AF:

0.00658

AC:

375

AN:

56954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

488

976

1465

1953

2441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.00654

AC:

995

AN:

152204

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

474

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41536

American (AMR)

AF:

0.00196

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00925

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

777

AN:

68006

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00853

Hom.:

Bravo

AF:

0.00592

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.00871

EpiControl

AF:

0.00961

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 31, 2018

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. -

Oct 14, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EVC: BP4, BP7, BS1, BS2 -

not specified

Benign:2

Oct 02, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ellis-van Creveld syndrome

Benign:2

Jan 12, 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. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.41

CADD

Benign

8.6

(source)

DANN

Benign

0.59

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism

(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