4-5748136-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_153717.3(EVC):​c.940-12C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000935 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

EVC
NM_153717.3 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0001983
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.216
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 4-5748136-C-G is Benign according to our data. Variant chr4-5748136-C-G is described in ClinVar as [Benign]. Clinvar id is 1653442.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EVCNM_153717.3 linkuse as main transcriptc.940-12C>G 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.940-12C>G splice_polypyrimidine_tract_variant, intron_variant 1 NM_153717.3 P1
EVCENST00000509451.1 linkuse as main transcriptc.940-12C>G splice_polypyrimidine_tract_variant, intron_variant 1
CRMP1ENST00000506216.5 linkuse as main transcriptn.1824G>C non_coding_transcript_exon_variant 13/135

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152190
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00404
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000258
AC:
65
AN:
251458
Hom.:
0
AF XY:
0.000272
AC XY:
37
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00343
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000841
AC:
123
AN:
1461844
Hom.:
0
Cov.:
31
AF XY:
0.0000825
AC XY:
60
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00189
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000629
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152308
Hom.:
0
Cov.:
34
AF XY:
0.000228
AC XY:
17
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00405
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000171
Hom.:
0
Bravo
AF:
0.000200
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
8.7
DANN
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00020
dbscSNV1_RF
Benign
0.056
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: rs200707006; hg19: chr4-5749863; API