dbSNP rs2247916: CPLX2:c.-502G>T (chr5-175796451-G-T) – 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.-502G>T 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 152,178 control chromosomes in the GnomAD database, including 2,748 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 ( 2748 hom., cov: 33)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

CPLX2
ENST00000359546.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.462

Publications

2 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

new If you want to explore the variant's impact on the transcript ENST00000359546.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.68).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359546.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX2	NM_006650.4		c.-502G>T		upstream_gene	N/A	NP_006641.1	Q6PUV4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPLX2	ENST00000359546.8	TSL:1	c.-502G>T	5_prime_UTR	Exon 1 of 5	ENSP00000352544.4	Q6PUV4
CPLX2	ENST00000899625.1		c.-169+123G>T	intron	N/A	ENSP00000569684.1
CPLX2	ENST00000899626.1		c.-422G>T	upstream_gene	N/A	ENSP00000569685.1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28385

AN:

152026

Hom.:

2745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.188

GnomAD4 exome

AF:

0.118

AC:

AN:

Hom.:

Cov.:

AF XY:

0.115

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.154

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.187

AC:

28396

AN:

152144

Hom.:

2748

Cov.:

AF XY:

0.185

AC XY:

13791

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.156

AC:

6485

AN:

41522

American (AMR)

AF:

0.186

AC:

2843

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3470

East Asian (EAS)

AF:

0.101

AC:

523

AN:

5178

South Asian (SAS)

AF:

0.246

AC:

1185

AN:

4818

European-Finnish (FIN)

AF:

0.168

AC:

1785

AN:

10596

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14384

AN:

67956

Other (OTH)

AF:

0.187

AC:

394

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1194

2389

3583

4778

5972

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:

0.196

Hom.:

502

Bravo

AF:

0.183

Asia WGS

AF:

0.183

AC:

637

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.9

(source)

DANN

Benign

0.76

PhyloP100

0.46

PromoterAI

0.030

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over