Variant 4-5745189-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 262782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5745189-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.802-15C>T		intron_variant		ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.802-15C>T		intron_variant		1	NM_153717.3	ENSP00000264956.6		P57679
EVC	ENST00000509451.1 link	c.802-15C>T		intron_variant		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

GnomAD3 exomes

AF:

0.597

AC:

141222

AN:

236632

Hom.:

44514

AF XY:

0.600

AC XY:

76935

AN XY:

128170

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 SAS exome

AF:

0.571

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

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.653

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.645

Gnomad4 OTH exome

AF:

0.618

GnomAD4 genome

AF:

0.603

AC:

83979

AN:

139342

Hom.:

23607

Cov.:

AF XY:

0.597

AC XY:

40714

AN XY:

68152

show subpopulations

Gnomad4 AFR

AF:

0.597

Gnomad4 AMR

AF:

0.529

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.638

Gnomad4 OTH

AF:

0.592

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 15, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2025

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Curry-Hall syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.16

DANN

Benign

0.37

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