rs871853

Positions:

• chr5-175855307-G-T

Variant summary

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

The ENST00000359546.8(CPLX2):​c.-88-23345G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,142 control chromosomes in the GnomAD database, including 36,891 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 0.69 (36891 hom., cov: 33)
• Consequence: CPLX2 ENST00000359546.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLX2	NM_006650.4	c.-88-23345G>T		intron_variant
CPLX2	XM_005265799.2	c.-88-23345G>T		intron_variant
CPLX2	XM_047416650.1	c.-88-23345G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLX2	ENST00000359546.8	c.-88-23345G>T		intron_variant		1		P1
CPLX2	ENST00000515502.1	c.-88-23345G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105056 AN: 152026 Hom.: 36848 Cov.: 33

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.654

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 105160 AN: 152142 Hom.: 36891 Cov.: 33 AF XY: 0.698 AC XY: 51886 AN XY: 74386

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.656

Alfa AF: 0.669 Hom.: 5765

Bravo AF: 0.694

Asia WGS AF: 0.789 AC: 2743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.53

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: rs871853; hg19: chr5-175282310;