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4-5808197-C-G

Variant summary

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

The NM_153717.3(EVC):​c.2562-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,554,030 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 129 hom., cov: 27)
Exomes 𝑓: 0.0027 ( 144 hom. )

Consequence

EVC
NM_153717.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00001961
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0400
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]
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]

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=-0.87).
BP6
Variant 4-5808197-C-G is Benign according to our data. Variant chr4-5808197-C-G is described in ClinVar as [Benign]. Clinvar id is 349206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EVCNM_153717.3 linkuse as main transcriptc.2562-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000264956.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EVCENST00000264956.11 linkuse as main transcriptc.2562-4C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_153717.3 P1
CRMP1ENST00000506216.5 linkuse as main transcriptn.1647+17297G>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0338
AC:
3305
AN:
97892
Hom.:
127
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.112
Gnomad AMI
AF:
0.0796
Gnomad AMR
AF:
0.0124
Gnomad ASJ
AF:
0.00367
Gnomad EAS
AF:
0.000244
Gnomad SAS
AF:
0.000327
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000623
Gnomad OTH
AF:
0.0248
GnomAD3 exomes
AF:
0.00627
AC:
1551
AN:
247556
Hom.:
55
AF XY:
0.00453
AC XY:
607
AN XY:
133960
show subpopulations
Gnomad AFR exome
AF:
0.0831
Gnomad AMR exome
AF:
0.00387
Gnomad ASJ exome
AF:
0.00190
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.000297
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000386
Gnomad OTH exome
AF:
0.00396
GnomAD4 exome
AF:
0.00265
AC:
3864
AN:
1456044
Hom.:
144
Cov.:
37
AF XY:
0.00238
AC XY:
1720
AN XY:
724166
show subpopulations
Gnomad4 AFR exome
AF:
0.0892
Gnomad4 AMR exome
AF:
0.00463
Gnomad4 ASJ exome
AF:
0.00216
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000407
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000133
Gnomad4 OTH exome
AF:
0.00722
GnomAD4 genome
AF:
0.0340
AC:
3328
AN:
97986
Hom.:
129
Cov.:
27
AF XY:
0.0333
AC XY:
1579
AN XY:
47352
show subpopulations
Gnomad4 AFR
AF:
0.113
Gnomad4 AMR
AF:
0.0123
Gnomad4 ASJ
AF:
0.00367
Gnomad4 EAS
AF:
0.000244
Gnomad4 SAS
AF:
0.000328
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000623
Gnomad4 OTH
AF:
0.0244
Alfa
AF:
0.00152
Hom.:
1

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 06, 2016This 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. -
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 29, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.55
DANN
Benign
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000020
dbscSNV1_RF
Benign
0.0
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.

Other links and lift over

dbSNP: rs60082311; hg19: chr4-5809924; API