5-175883811-C-G

Position:

• chr5-175883811-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLX2	NM_001008220.2	c.*3766C>G		3_prime_UTR_variant	4/4	ENST00000393745.8	NP_001008221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000393745.8	c.*3766C>G		3_prime_UTR_variant	4/4	1	NM_001008220.2	ENSP00000377346.3
CPLX2	ENST00000359546.8	c.*3766C>G		3_prime_UTR_variant	5/5	1		ENSP00000352544.4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84150 AN: 151818 Hom.: 24233 Cov.: 32

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.: 0 AF XY: 0.577 AC XY: 210 AN XY: 364

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.658

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.554 AC: 84190 AN: 151936 Hom.: 24245 Cov.: 32 AF XY: 0.562 AC XY: 41733 AN XY: 74258

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.542

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.021
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs930047; hg19: chr5-175310814;