rs2247916

Positions:

• chr5-175796451-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.175796451G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000359546.8	c.-502G>T		5_prime_UTR_variant	1/5	1		ENSP00000352544.4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28385 AN: 152026 Hom.: 2745 Cov.: 33

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: 4 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.115 AC XY: 3 AN XY: 26

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.154

GnomAD4 genome AF: 0.187 AC: 28396 AN: 152144 Hom.: 2748 Cov.: 33 AF XY: 0.185 AC XY: 13791 AN XY: 74398

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.187

Alfa AF: 0.197 Hom.: 491

Bravo AF: 0.183

Asia WGS AF: 0.183 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.76

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: rs2247916; hg19: chr5-175223454;