Variant chr4-786598-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006651.4(CPLX1):c.308C>T(p.Pro103Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000664 in 1,612,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000067 ( 1 hom. )

Consequence

CPLX1
NM_006651.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.03

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]

CPLX1 links:

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 (MetaRNN=0.012136221).

BP6

Variant 4-786598-G-A is Benign according to our data. Variant chr4-786598-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 736367.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLX1	NM_006651.4 linkuse as main transcript	c.308C>T	p.Pro103Leu	missense_variant	4/4	ENST00000304062.11
CPLX1	XM_011513391.2 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CPLX1	ENST00000304062.11 linkuse as main transcript	c.308C>T	p.Pro103Leu	missense_variant	4/4	1	NM_006651.4	P1
CPLX1	ENST00000505203.1 linkuse as main transcript	c.245C>T	p.Pro82Leu	missense_variant	5/5	2
CPLX1	ENST00000504062.1 linkuse as main transcript	c.263C>T	p.Pro88Leu	missense_variant	3/3	3
CPLX1	ENST00000506404.1 linkuse as main transcript	n.361C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000224

AC:

AN:

245714

Hom.:

AF XY:

0.000202

AC XY:

AN XY:

133832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00290

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000671

AC:

AN:

1460064

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00199

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000215

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.074

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.0

N;D;N

REVEL

Benign

0.037

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.16

B;B;.

Vest4

0.17

MutPred

0.27

Loss of glycosylation at K98 (P = 0.0355);.;.;

MVP

0.14

MPC

0.49

ClinPred

0.098

GERP RS

3.6

Varity_R

0.094

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over