5-175817031-C-T

Variant names:

• chr5-175817031-C-T
• rs7448069
• ENST00000359546.8:c.-89+7963C>T

Variant summary

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

The NM_006650.4(CPLX2):​c.-89+7963C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,320 control chromosomes in the GnomAD database, including 275 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 0.050 (275 hom., cov: 33)
• Consequence: CPLX2 NM_006650.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006650.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX2	NM_006650.4		c.-89+7963C>T		intron	N/A	NP_006641.1	Q6PUV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX2	ENST00000359546.8	TSL:1	c.-89+7963C>T		intron	N/A	ENSP00000352544.4	Q6PUV4
	CPLX2	ENST00000899625.1		c.-89+7963C>T		intron	N/A	ENSP00000569684.1
	CPLX2	ENST00000899626.1		c.-89+20247C>T		intron	N/A	ENSP00000569685.1

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7682 AN: 152202 Hom.: 275 Cov.: 33

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0504 AC: 7683 AN: 152320 Hom.: 275 Cov.: 33 AF XY: 0.0497 AC XY: 3700 AN XY: 74472

African (AFR) AF: 0.0123 AC: 512 AN: 41592

American (AMR) AF: 0.0431 AC: 659 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4824

European-Finnish (FIN) AF: 0.0974 AC: 1033 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5119 AN: 68024

Other (OTH) AF: 0.0459 AC: 97 AN: 2112

Alfa AF: 0.0450 Hom.: 142

Bravo AF: 0.0453

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.13
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: rs7448069; hg19: chr5-175244034;