5-175804203-C-T

Variant names:

• chr5-175804203-C-T
• rs890736
• ENST00000359546.8:c.-168-4786C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359546.8(CPLX2):​c.-168-4786C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,204 control chromosomes in the GnomAD database, including 50,132 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 0.81 (50132 hom., cov: 33)
• Consequence: CPLX2 ENST00000359546.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLX2	NM_006650.4	c.-168-4786C>T		intron_variant	Intron 1 of 4		NP_006641.1
CPLX2	XM_005265799.2	c.-89+7419C>T		intron_variant	Intron 1 of 3		XP_005265856.1
CPLX2	XM_047416650.1	c.-346-1241C>T		intron_variant	Intron 1 of 5		XP_047272606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000359546.8	c.-168-4786C>T		intron_variant	Intron 1 of 4	1		ENSP00000352544.4
CPLX2	ENST00000515502.1	c.-406-1241C>T		intron_variant	Intron 1 of 4	4		ENSP00000423564.1
CPLX2	ENST00000506642.5	n.158-4786C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123343 AN: 152086 Hom.: 50082 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.811 AC: 123448 AN: 152204 Hom.: 50132 Cov.: 33 AF XY: 0.812 AC XY: 60457 AN XY: 74422

African (AFR) AF: 0.839 AC: 34832 AN: 41522

American (AMR) AF: 0.814 AC: 12462 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2884 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4435 AN: 5168

South Asian (SAS) AF: 0.756 AC: 3647 AN: 4826

European-Finnish (FIN) AF: 0.835 AC: 8849 AN: 10600

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53629 AN: 67992

Other (OTH) AF: 0.811 AC: 1716 AN: 2116

Alfa AF: 0.797 Hom.: 204642

Bravo AF: 0.814

Asia WGS AF: 0.792 AC: 2754 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	0.069
DANN	Benign	0.45
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs890736; hg19: chr5-175231206;