ENST00000359546.8:c.-88-30170T>C

Variant names:

• chr5-175848482-T-C
• rs13174727
• ENST00000359546.8:c.-88-30170T>C

Variant summary

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

The ENST00000359546.8(CPLX2):​c.-88-30170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,048 control chromosomes in the GnomAD database, including 1,197 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 0.11 (1197 hom., cov: 32)
• Consequence: CPLX2 ENST00000359546.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLX2	NM_006650.4	c.-88-30170T>C		intron_variant	Intron 2 of 4		NP_006641.1
CPLX2	XM_005265799.2	c.-88-30170T>C		intron_variant	Intron 1 of 3		XP_005265856.1
CPLX2	XM_047416650.1	c.-88-30170T>C		intron_variant	Intron 3 of 5		XP_047272606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000359546.8	c.-88-30170T>C		intron_variant	Intron 2 of 4	1		ENSP00000352544.4
CPLX2	ENST00000515502.1	c.-88-30170T>C		intron_variant	Intron 4 of 4	4		ENSP00000423564.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16148 AN: 151928 Hom.: 1201 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.106 AC: 16139 AN: 152048 Hom.: 1197 Cov.: 32 AF XY: 0.102 AC XY: 7567 AN XY: 74328

African (AFR) AF: 0.0285 AC: 1181 AN: 41484

American (AMR) AF: 0.108 AC: 1654 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5168

South Asian (SAS) AF: 0.0699 AC: 336 AN: 4804

European-Finnish (FIN) AF: 0.0920 AC: 972 AN: 10568

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10713 AN: 67962

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.145 Hom.: 3010

Bravo AF: 0.104

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.91
DANN	Benign	0.26
PhyloP100		-0.52
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: rs13174727; hg19: chr5-175275485;