Genetic Variant CPLX2:c.*3766C>G (chr5-175883811-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001008220.2(CPLX2):c.*3766C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,478 control chromosomes in the GnomAD database, including 24,347 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 0.55 ( 24245 hom., cov: 32)

Exomes 𝑓: 0.61 ( 102 hom. )

Consequence

CPLX2
NM_001008220.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Publications

7 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008220.2. 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_001008220.2	MANE Select	c.*3766C>G		3_prime_UTR	Exon 4 of 4	NP_001008221.1	Q6PUV4
	CPLX2	NM_006650.4		c.*3766C>G		3_prime_UTR	Exon 5 of 5	NP_006641.1	Q6PUV4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPLX2	ENST00000393745.8	TSL:1 MANE Select	c.*3766C>G	3_prime_UTR	Exon 4 of 4	ENSP00000377346.3	Q6PUV4
CPLX2	ENST00000359546.8	TSL:1	c.*3766C>G	3_prime_UTR	Exon 5 of 5	ENSP00000352544.4	Q6PUV4
CPLX2	ENST00000899625.1		c.*3766C>G	3_prime_UTR	Exon 5 of 5	ENSP00000569684.1

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84150

AN:

151818

Hom.:

24233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.633

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.539

GnomAD4 exome

AF:

0.605

AC:

328

AN:

542

Hom.:

102

Cov.:

AF XY:

0.577

AC XY:

210

AN XY:

364

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.658

AC:

254

AN:

386

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.439

AC:

AN:

132

Other (OTH)

AF:

0.875

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.554

AC:

84190

AN:

151936

Hom.:

24245

Cov.:

AF XY:

0.562

AC XY:

41733

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.409

AC:

16938

AN:

41452

American (AMR)

AF:

0.633

AC:

9667

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1632

AN:

3468

East Asian (EAS)

AF:

0.766

AC:

3932

AN:

5130

South Asian (SAS)

AF:

0.568

AC:

2737

AN:

4816

European-Finnish (FIN)

AF:

0.709

AC:

7499

AN:

10574

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40085

AN:

67918

Other (OTH)

AF:

0.542

AC:

1144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1837

3674

5510

7347

9184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.456

Hom.:

1364

Bravo

AF:

0.545

Asia WGS

AF:

0.676

AC:

2348

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.021

(source)

DANN

Benign

0.48

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over