Genetic Variant ENST00000359546.8:c.-340G>A (chr5-175796613-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000359546.8(CPLX2):c.-340G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,508 control chromosomes in the GnomAD database, including 2,771 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 2766 hom., cov: 33)

Exomes 𝑓: 0.19 ( 5 hom. )

Consequence

CPLX2
ENST00000359546.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

Publications

6 publications found

Variant links:

Genes affected

CPLX2 (HGNC:2310): (complexin 2) 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. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

CPLX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CPLX2	NM_006650.4 link	c.-340G>A	5_prime_UTR_variant	Exon 1 of 5	NP_006641.1	Q6PUV4
CPLX2	XM_005265799.2 link	c.-260G>A	5_prime_UTR_variant	Exon 1 of 4	XP_005265856.1	Q6PUV4
CPLX2	XM_047416650.1 link	c.-518G>A	5_prime_UTR_variant	Exon 1 of 6	XP_047272606.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CPLX2	ENST00000359546.8 link	c.-340G>A	5_prime_UTR_variant	Exon 1 of 5	1	ENSP00000352544.4	Q6PUV4
CPLX2	ENST00000515502.1 link	c.-578G>A	upstream_gene_variant		4	ENSP00000423564.1
CPLX2	ENST00000506642.5 link	n.-15G>A	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28471

AN:

152138

Hom.:

2763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0995

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.187

AC:

AN:

252

Hom.:

Cov.:

AF XY:

0.191

AC XY:

AN XY:

188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.181

AC:

AN:

204

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.187

AC:

28482

AN:

152256

Hom.:

2766

Cov.:

AF XY:

0.185

AC XY:

13808

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.156

AC:

6496

AN:

41558

American (AMR)

AF:

0.187

AC:

2856

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

585

AN:

3472

East Asian (EAS)

AF:

0.100

AC:

517

AN:

5162

South Asian (SAS)

AF:

0.241

AC:

1163

AN:

4828

European-Finnish (FIN)

AF:

0.170

AC:

1800

AN:

10616

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14457

AN:

68002

Other (OTH)

AF:

0.187

AC:

396

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1252

2504

3757

5009

6261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.203

Hom.:

3139

Bravo

AF:

0.183

Asia WGS

AF:

0.182

AC:

634

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

(source)

DANN

Benign

0.60

PhyloP100

0.014

PromoterAI

-0.0092

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over