chr2-85581748-C-T

Variant names:

• chr2-85581748-C-T
• rs1058588
• NM_003761.5:c.*32C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 57 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP8	NM_003761.5	MANE Select	c.*32C>T		3_prime_UTR	Exon 3 of 3	NP_003752.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP8	ENST00000263864.10	TSL:1 MANE Select	c.*32C>T		3_prime_UTR	Exon 3 of 3	ENSP00000263864.5
	VAMP8	ENST00000409760.1	TSL:3	c.*168C>T		3_prime_UTR	Exon 4 of 4	ENSP00000387094.1
	VAMP8	ENST00000432071.1	TSL:3	c.*32C>T		3_prime_UTR	Exon 3 of 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

GnomAD2 exomes AF: 0.398 AC: 99802 AN: 250570 AF XY: 0.401

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 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

African (AFR) AF: 0.474 AC: 15854 AN: 33418

American (AMR) AF: 0.303 AC: 13516 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9644 AN: 26082

East Asian (EAS) AF: 0.380 AC: 15066 AN: 39676

South Asian (SAS) AF: 0.377 AC: 32463 AN: 86150

European-Finnish (FIN) AF: 0.427 AC: 22787 AN: 53326

Middle Eastern (MID) AF: 0.371 AC: 2140 AN: 5766

European-Non Finnish (NFE) AF: 0.422 AC: 469364 AN: 1110940

Other (OTH) AF: 0.420 AC: 25327 AN: 60332

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

African (AFR) AF: 0.478 AC: 19791 AN: 41438

American (AMR) AF: 0.368 AC: 5616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2022 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1830 AN: 4826

European-Finnish (FIN) AF: 0.440 AC: 4648 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28425 AN: 67948

Other (OTH) AF: 0.419 AC: 885 AN: 2112

Alfa AF: 0.416 Hom.: 22374

Bravo AF: 0.425

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.44
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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