rs4642178

chr4-5756217-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153717.3(EVC):c.1465-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,469,970 control chromosomes in the GnomAD database, including 33,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3182 hom., cov: 31)
  • Exomes 𝑓: 0.21 (30211 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.637

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-5756217-A-C is Benign according to our data. Variant chr4-5756217-A-C is described in ClinVar as [Benign]. Clinvar id is 262767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.1465-47A>C		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.1465-47A>C		intron_variant		1	NM_153717.3	P1
EVC	ENST00000509451.1	c.1465-47A>C		intron_variant		1
CRMP1	ENST00000506216.5	n.1648-7905T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30622 AN: 151516 Hom.: 3178 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.223 AC: 38362 AN: 172142 Hom.: 4530 AF XY: 0.222 AC XY: 20169 AN XY: 90950

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.191

Gnomad SAS exome AF: 0.221

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.209 AC: 275309 AN: 1318336 Hom.: 30211 Cov.: 19 AF XY: 0.210 AC XY: 137555 AN XY: 656224

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.202 AC: 30652 AN: 151634 Hom.: 3182 Cov.: 31 AF XY: 0.205 AC XY: 15172 AN XY: 74074

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.205

Alfa AF: 0.199 Hom.: 557

Bravo AF: 0.202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Ellis-van Creveld syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.28
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs4642178; hg19: chr4-5757944; COSMIC: COSV53840096; COSMIC: COSV53840096;