rs890737

Positions:

• chr5-175858895-G-A
• chr5-175858895-G-T

Variant summary

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

The ENST00000359546.8(CPLX2):​c.-88-19757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,146 control chromosomes in the GnomAD database, including 24,888 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 0.56 (24888 hom., cov: 33)
• Consequence: CPLX2 ENST00000359546.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLX2	NM_006650.4	c.-88-19757G>A		intron_variant			NP_006641.1
CPLX2	XM_005265799.2	c.-88-19757G>A		intron_variant			XP_005265856.1
CPLX2	XM_047416650.1	c.-88-19757G>A		intron_variant			XP_047272606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000359546.8	c.-88-19757G>A		intron_variant		1		ENSP00000352544	P1
CPLX2	ENST00000515502.1	c.-88-19757G>A		intron_variant		4		ENSP00000423564

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85268 AN: 152028 Hom.: 24873 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.561 AC: 85332 AN: 152146 Hom.: 24888 Cov.: 33 AF XY: 0.569 AC XY: 42353 AN XY: 74384

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.538

Alfa AF: 0.571 Hom.: 3147

Bravo AF: 0.550

Asia WGS AF: 0.660 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.49

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: rs890737; hg19: chr5-175285898;