rs1058588

Positions:

• chr2-85581748-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003761.5(VAMP8):​c.*32C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,612,360 control chromosomes in the GnomAD database, including 140,627 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 0.43 (14004 hom., cov: 31)
  • Exomes 𝑓: 0.42 (126623 hom.)
• Consequence: VAMP8 NM_003761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

Genes affected

VAMP8 (HGNC:12647): (vesicle associated membrane protein 8) This gene encodes an integral membrane protein that belongs to the synaptobrevin/vesicle-associated membrane protein subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The encoded protein is involved in the fusion of synaptic vesicles with the presynaptic membrane.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP8	NM_003761.5	c.*32C>T		3_prime_UTR_variant	3/3	ENST00000263864.10	NP_003752.2
VAMP8	XM_017005170.2	c.*168C>T		3_prime_UTR_variant	4/4		XP_016860659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP8	ENST00000263864.10	c.*32C>T		3_prime_UTR_variant	3/3	1	NM_003761.5	ENSP00000263864.5
VAMP8	ENST00000409760.1	c.*168C>T		3_prime_UTR_variant	4/4	3		ENSP00000387094.1
VAMP8	ENST00000432071.1	c.*32C>T		3_prime_UTR_variant	3/3	3		ENSP00000407984.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64943 AN: 151886 Hom.: 13988 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.416

GnomAD3 exomes AF: 0.398 AC: 99802 AN: 250570 Hom.: 20284 AF XY: 0.401 AC XY: 54333 AN XY: 135426

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.384

Gnomad SAS exome AF: 0.374

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.415 AC: 606161 AN: 1460356 Hom.: 126623 Cov.: 35 AF XY: 0.415 AC XY: 301285 AN XY: 726534

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.428 AC: 64994 AN: 152004 Hom.: 14004 Cov.: 31 AF XY: 0.427 AC XY: 31705 AN XY: 74304

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.419

Alfa AF: 0.415 Hom.: 15901

Bravo AF: 0.425

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1058588; hg19: chr2-85808871; COSMIC: COSV55705141; COSMIC: COSV55705141;