5-175817279-G-A

Position:

• chr5-175817279-G-A

Variant summary

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

The NM_006650.4(CPLX2):​c.-89+8211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,194 control chromosomes in the GnomAD database, including 44,292 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 0.76 (44292 hom., cov: 33)
• Consequence: CPLX2 NM_006650.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLX2	NM_006650.4	c.-89+8211G>A		intron_variant			NP_006641.1
CPLX2	XM_005265799.2	c.-89+20495G>A		intron_variant			XP_005265856.1
CPLX2	XM_047416650.1	c.-89+8211G>A		intron_variant			XP_047272606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000359546.8	c.-89+8211G>A		intron_variant		1		ENSP00000352544.4
CPLX2	ENST00000515502.1	c.-89+7887G>A		intron_variant		4		ENSP00000423564.1
CPLX2	ENST00000506642.5	n.237+8211G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115745 AN: 152076 Hom.: 44251 Cov.: 33

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.761 AC: 115843 AN: 152194 Hom.: 44292 Cov.: 33 AF XY: 0.766 AC XY: 56996 AN XY: 74420

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.763

Alfa AF: 0.761 Hom.: 61576

Bravo AF: 0.763

Asia WGS AF: 0.874 AC: 3039 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.73
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2382121; hg19: chr5-175244282;