chr4-5748276-A-G

Variant names:

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	NM_153717.3	MANE Select	c.1068A>G	p.Leu356Leu	synonymous	Exon 8 of 21	NP_714928.1
	EVC	NM_001306090.2		c.1068A>G	p.Leu356Leu	synonymous	Exon 8 of 21	NP_001293019.1
	EVC	NM_001306092.2		c.1068A>G	p.Leu356Leu	synonymous	Exon 8 of 12	NP_001293021.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.1068A>G	p.Leu356Leu	synonymous	Exon 8 of 21	ENSP00000264956.6
	EVC	ENST00000509451.1	TSL:1	c.1068A>G	p.Leu356Leu	synonymous	Exon 8 of 12	ENSP00000426774.1
	EVC	ENST00000861182.1		c.1068A>G	p.Leu356Leu	synonymous	Exon 8 of 21	ENSP00000531241.1

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Ellis-van Creveld syndrome (4)
-	-	2	not specified (2)
-	-	1	Curry-Hall syndrome (1)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;