5-175880253-T-C

Variant names:

• chr5-175880253-T-C
• rs3822674
• NM_001008220.2:c.*208T>C

Variant summary

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

The NM_001008220.2(CPLX2):​c.*208T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 683,570 control chromosomes in the GnomAD database, including 85,443 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 0.49 (18426 hom., cov: 32)
  • Exomes 𝑓: 0.50 (67017 hom.)
• Consequence: CPLX2 NM_001008220.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLX2	NM_001008220.2	c.*208T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000393745.8	NP_001008221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLX2	ENST00000393745.8	c.*208T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001008220.2	ENSP00000377346.3
CPLX2	ENST00000359546.8	c.*208T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000352544.4
CPLX2	ENST00000515094.1	c.*208T>C		downstream_gene_variant		4		ENSP00000421825.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74021 AN: 151778 Hom.: 18410 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.513 AC: 67666 AN: 131962 AF XY: 0.505

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.571

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.499 AC: 265192 AN: 531674 Hom.: 67017 Cov.: 5 AF XY: 0.495 AC XY: 141923 AN XY: 286988

African (AFR) AF: 0.437 AC: 6369 AN: 14564

American (AMR) AF: 0.579 AC: 17946 AN: 30994

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 7500 AN: 18330

East Asian (EAS) AF: 0.588 AC: 17751 AN: 30210

South Asian (SAS) AF: 0.457 AC: 27121 AN: 59302

European-Finnish (FIN) AF: 0.597 AC: 24209 AN: 40542

Middle Eastern (MID) AF: 0.335 AC: 1299 AN: 3882

European-Non Finnish (NFE) AF: 0.489 AC: 149133 AN: 305092

Other (OTH) AF: 0.482 AC: 13864 AN: 28758

GnomAD4 genome AF: 0.488 AC: 74073 AN: 151896 Hom.: 18426 Cov.: 32 AF XY: 0.492 AC XY: 36503 AN XY: 74236

African (AFR) AF: 0.440 AC: 18243 AN: 41438

American (AMR) AF: 0.535 AC: 8173 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3468

East Asian (EAS) AF: 0.574 AC: 2942 AN: 5122

South Asian (SAS) AF: 0.461 AC: 2214 AN: 4802

European-Finnish (FIN) AF: 0.614 AC: 6486 AN: 10570

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.489 AC: 33221 AN: 67910

Other (OTH) AF: 0.451 AC: 953 AN: 2112

Alfa AF: 0.482 Hom.: 24824

Bravo AF: 0.484

Asia WGS AF: 0.549 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.0030
Mutation Taster		=99/1	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: rs3822674; hg19: chr5-175307256; COSMIC: COSV63999511; COSMIC: COSV63999511;