rs2291151

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.*14G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,600,302 control chromosomes in the GnomAD database, including 294,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27977 hom., cov: 33)

Exomes 𝑓: 0.60 ( 266080 hom. )

Consequence

EVC
NM_153717.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.778

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 4-5811051-G-A is Benign according to our data. Variant chr4-5811051-G-A is described in ClinVar as [Benign]. Clinvar id is 262759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5811051-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC	NM_153717.3 linkuse as main transcript	c.*14G>A		3_prime_UTR_variant	21/21	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 linkuse as main transcript	c.*14G>A		3_prime_UTR_variant	21/21	1	NM_153717.3	ENSP00000264956	P1
CRMP1	ENST00000506216.5 linkuse as main transcript	n.1647+14443C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91736

AN:

151946

Hom.:

27948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.627

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.613

Gnomad OTH

AF:

0.589

GnomAD3 exomes

AF:

0.579

AC:

136742

AN:

236022

Hom.:

40579

AF XY:

0.587

AC XY:

74686

AN XY:

127314

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.446

Gnomad ASJ exome

AF:

0.600

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.615

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.603

AC:

872793

AN:

1448238

Hom.:

266080

Cov.:

AF XY:

0.604

AC XY:

434708

AN XY:

719906

show subpopulations

Gnomad4 AFR exome

AF:

0.628

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.603

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.682

Gnomad4 NFE exome

AF:

0.612

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.604

AC:

91810

AN:

152064

Hom.:

27977

Cov.:

AF XY:

0.604

AC XY:

44904

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.627

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.331

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.701

Gnomad4 NFE

AF:

0.613

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.575

Hom.:

6288

Bravo

AF:

0.586

Asia WGS

AF:

0.484

AC:

1688

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

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Ellis-van Creveld syndrome

Benign:2

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	Genome-Nilou Lab	Jul 30, 2021	- -

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

-0.94

CADD

Benign

0.26

DANN

Benign

0.54

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