chr4-786501-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_006651.4(CPLX1):​c.405G>A​(p.Ter135Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,573,926 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CPLX1
NM_006651.4 stop_retained

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0800
Variant links:
Genes affected
CPLX1 (HGNC:2309): (complexin 1) Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 4-786501-C-T is Benign according to our data. Variant chr4-786501-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1961631.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.08 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPLX1NM_006651.4 linkc.405G>A p.Ter135Ter stop_retained_variant Exon 4 of 4 ENST00000304062.11 NP_006642.1 O14810
CPLX1XM_011513391.2 linkc.360G>A p.Ter120Ter stop_retained_variant Exon 3 of 3 XP_011511693.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPLX1ENST00000304062.11 linkc.405G>A p.Ter135Ter stop_retained_variant Exon 4 of 4 1 NM_006651.4 ENSP00000305613.6 O14810
CPLX1ENST00000505203.1 linkc.342G>A p.Ter114Ter stop_retained_variant Exon 5 of 5 2 ENSP00000425960.1 D6RI11
CPLX1ENST00000506404.1 linkn.458G>A non_coding_transcript_exon_variant Exon 2 of 2 2
CPLX1ENST00000504062.1 linkc.*30G>A downstream_gene_variant 3 ENSP00000421947.1 D6RAG3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000101
AC:
2
AN:
198230
Hom.:
0
AF XY:
0.0000186
AC XY:
2
AN XY:
107710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000234
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000373
AC:
53
AN:
1421942
Hom.:
0
Cov.:
36
AF XY:
0.0000412
AC XY:
29
AN XY:
703242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000486
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151984
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not provided Benign:1
Feb 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely 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
-0.58
CADD
Benign
6.6
DANN
Benign
0.91

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs377210149; hg19: chr4-780289; COSMIC: COSV58376450; COSMIC: COSV58376450; API