rs4642178

Variant names:

• chr4-5756217-A-C
• rs4642178
• NM_153717.3:c.1465-47A>C

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.637
• Publications: 2 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 -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 VariationId 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 rank	MANE	Protein	UniProt
EVC	NM_153717.3	c.1465-47A>C		intron_variant	Intron 10 of 20	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.1465-47A>C		intron_variant	Intron 10 of 20	1	NM_153717.3	ENSP00000264956.6
EVC	ENST00000509451.1	c.1465-47A>C		intron_variant	Intron 10 of 11	1		ENSP00000426774.1
CRMP1	ENST00000506216.5	n.1648-7905T>G		intron_variant	Intron 12 of 12	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

GnomAD2 exomes AF: 0.223 AC: 38362 AN: 172142 AF XY: 0.222

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 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

African (AFR) AF: 0.162 AC: 4957 AN: 30620

American (AMR) AF: 0.291 AC: 10690 AN: 36688

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4163 AN: 24656

East Asian (EAS) AF: 0.187 AC: 7048 AN: 37660

South Asian (SAS) AF: 0.222 AC: 17027 AN: 76540

European-Finnish (FIN) AF: 0.242 AC: 11975 AN: 49518

Middle Eastern (MID) AF: 0.249 AC: 1372 AN: 5520

European-Non Finnish (NFE) AF: 0.206 AC: 206846 AN: 1001752

Other (OTH) AF: 0.203 AC: 11231 AN: 55382

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

African (AFR) AF: 0.160 AC: 6605 AN: 41364

American (AMR) AF: 0.250 AC: 3808 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3466

East Asian (EAS) AF: 0.181 AC: 933 AN: 5150

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4806

European-Finnish (FIN) AF: 0.224 AC: 2338 AN: 10420

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14618 AN: 67870

Other (OTH) AF: 0.205 AC: 433 AN: 2108

Alfa AF: 0.199 Hom.: 557

Bravo AF: 0.202

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome Benign:1

Jun 15, 2021

Pars Genome 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	-0.88
CADD	Benign	0.28
DANN	Benign	0.66
PhyloP100		-0.64
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: rs4642178; hg19: chr4-5757944; COSMIC: COSV53840096; COSMIC: COSV53840096;