ENST00000359546.8:c.-89+8211G>A

Variant names:

• chr5-175817279-G-A
• rs2382121
• ENST00000359546.8:c.-89+8211G>A

Variant summary

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

The ENST00000359546.8(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 ENST00000359546.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• 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=-0.97).
• 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 rank	MANE	Protein	UniProt
CPLX2	NM_006650.4	c.-89+8211G>A		intron_variant	Intron 2 of 4		NP_006641.1
CPLX2	XM_005265799.2	c.-89+20495G>A		intron_variant	Intron 1 of 3		XP_005265856.1
CPLX2	XM_047416650.1	c.-89+8211G>A		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.-89+8211G>A		intron_variant	Intron 2 of 4	1		ENSP00000352544.4
CPLX2	ENST00000515502.1	c.-89+7887G>A		intron_variant	Intron 4 of 4	4		ENSP00000423564.1
CPLX2	ENST00000506642.5	n.237+8211G>A		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.722 AC: 29998 AN: 41528

American (AMR) AF: 0.824 AC: 12614 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2704 AN: 3468

East Asian (EAS) AF: 0.931 AC: 4819 AN: 5178

South Asian (SAS) AF: 0.856 AC: 4134 AN: 4828

European-Finnish (FIN) AF: 0.755 AC: 7996 AN: 10590

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51255 AN: 67988

Other (OTH) AF: 0.763 AC: 1609 AN: 2108

Alfa AF: 0.762 Hom.: 84980

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
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2382121; hg19: chr5-175244282;