rs33929747

Variant names:

• chr4-5748276-A-G
• rs33929747
• NM_153717.3:c.1068A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-5748276-A-G
• chr4-5748276-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_153717.3(EVC):​c.1068A>G​(p.Leu356Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,844 control chromosomes in the GnomAD database, including 83,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6401 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77331 hom.)
• Consequence: EVC NM_153717.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.912
• Publications: 18 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-5748276-A-G is Benign according to our data. Variant chr4-5748276-A-G is described in ClinVar as Benign. ClinVar VariationId is 262762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.912 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3	c.1068A>G	p.Leu356Leu	synonymous_variant	Exon 8 of 21	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.1068A>G	p.Leu356Leu	synonymous_variant	Exon 8 of 21	1	NM_153717.3	ENSP00000264956.6
EVC	ENST00000509451.1	c.1068A>G	p.Leu356Leu	synonymous_variant	Exon 8 of 12	1		ENSP00000426774.1
CRMP1	ENST00000506216.5	n.1684T>C		non_coding_transcript_exon_variant	Exon 13 of 13	5

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40538 AN: 151974 Hom.: 6406 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.298 AC: 74813 AN: 251348 AF XY: 0.296

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.319 AC: 466536 AN: 1461752 Hom.: 77331 Cov.: 49 AF XY: 0.316 AC XY: 229622 AN XY: 727166

African (AFR) AF: 0.0932 AC: 3119 AN: 33478

American (AMR) AF: 0.333 AC: 14884 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10696 AN: 26136

East Asian (EAS) AF: 0.171 AC: 6807 AN: 39698

South Asian (SAS) AF: 0.191 AC: 16481 AN: 86256

European-Finnish (FIN) AF: 0.301 AC: 16061 AN: 53396

Middle Eastern (MID) AF: 0.324 AC: 1869 AN: 5768

European-Non Finnish (NFE) AF: 0.340 AC: 377633 AN: 1111918

Other (OTH) AF: 0.314 AC: 18986 AN: 60386

GnomAD4 genome AF: 0.267 AC: 40547 AN: 152092 Hom.: 6401 Cov.: 32 AF XY: 0.263 AC XY: 19533 AN XY: 74342

African (AFR) AF: 0.104 AC: 4310 AN: 41526

American (AMR) AF: 0.347 AC: 5311 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3468

East Asian (EAS) AF: 0.188 AC: 967 AN: 5156

South Asian (SAS) AF: 0.196 AC: 946 AN: 4826

European-Finnish (FIN) AF: 0.290 AC: 3065 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23549 AN: 67950

Other (OTH) AF: 0.289 AC: 611 AN: 2114

Alfa AF: 0.322 Hom.: 6457

Bravo AF: 0.264

Asia WGS AF: 0.176 AC: 615 AN: 3478

EpiCase AF: 0.354

EpiControl AF: 0.344

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ellis-van Creveld syndrome Benign:4

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

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

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

- -

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	-0.89
CADD	Benign	2.1
DANN	Benign	0.50
PhyloP100		-0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs33929747; hg19: chr4-5750003; COSMIC: COSV53830469; COSMIC: COSV53830469;