Variant chr4-786498-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006651.4(CPLX1):c.*3G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,565,414 control chromosomes in the GnomAD database, including 519,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55037 hom., cov: 31)

Exomes 𝑓: 0.81 ( 464712 hom. )

Consequence

CPLX1
NM_006651.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.911

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-786498-C-G is Benign according to our data. Variant chr4-786498-C-G is described in ClinVar as [Benign]. Clinvar id is 1185526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLX1	NM_006651.4 linkuse as main transcript	c.*3G>C		3_prime_UTR_variant	4/4	ENST00000304062.11
CPLX1	XM_011513391.2 linkuse as main transcript	c.*3G>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CPLX1	ENST00000304062.11 linkuse as main transcript	c.*3G>C	3_prime_UTR_variant	4/4	1	NM_006651.4	P1
CPLX1	ENST00000505203.1 linkuse as main transcript	c.*3G>C	3_prime_UTR_variant	5/5	2
CPLX1	ENST00000506404.1 linkuse as main transcript	n.461G>C	non_coding_transcript_exon_variant	2/2	2
CPLX1	ENST00000504062.1 linkuse as main transcript		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128737

AN:

151806

Hom.:

54994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.772

Gnomad ASJ

AF:

0.789

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.841

Gnomad MID

AF:

0.850

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.824

GnomAD3 exomes

AF:

0.800

AC:

152446

AN:

190548

Hom.:

61371

AF XY:

0.802

AC XY:

83058

AN XY:

103546

show subpopulations

Gnomad AFR exome

AF:

0.961

Gnomad AMR exome

AF:

0.726

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.710

Gnomad SAS exome

AF:

0.811

Gnomad FIN exome

AF:

0.833

Gnomad NFE exome

AF:

0.811

Gnomad OTH exome

AF:

0.807

GnomAD4 exome

AF:

0.810

AC:

1144767

AN:

1413498

Hom.:

464712

Cov.:

AF XY:

0.810

AC XY:

565710

AN XY:

698354

show subpopulations

Gnomad4 AFR exome

AF:

0.963

Gnomad4 AMR exome

AF:

0.729

Gnomad4 ASJ exome

AF:

0.781

Gnomad4 EAS exome

AF:

0.720

Gnomad4 SAS exome

AF:

0.815

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.810

Gnomad4 OTH exome

AF:

0.813

GnomAD4 genome

AF:

0.848

AC:

128830

AN:

151916

Hom.:

55037

Cov.:

AF XY:

0.848

AC XY:

62946

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.956

Gnomad4 AMR

AF:

0.771

Gnomad4 ASJ

AF:

0.789

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.830

Gnomad4 FIN

AF:

0.841

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.825

Alfa

AF:

0.823

Hom.:

16563

Bravo

AF:

0.843

Asia WGS

AF:

0.805

AC:

2795

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2019

- -

Developmental and epileptic encephalopathy, 63

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

9.0

DANN

Benign

0.73

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