rs1150

Positions:

• chr17-8159265-A-G
• chr17-8159265-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014232.3(VAMP2):​c.*1590T>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 0.669 in 151,260 control chromosomes in the GnomAD database, including 34,117 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 0.67 (34105 hom., cov: 27)
  • Exomes 𝑓: 0.79 (12 hom.)
• Consequence: VAMP2 NM_014232.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

Genes affected

VAMP2 (HGNC:12643): (vesicle associated membrane protein 2) The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. This gene is thought to participate in neurotransmitter release at a step between docking and fusion. The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and synaptotagmin. It also forms a distinct complex with synaptophysin. It is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP2	NM_014232.3	c.*1590T>C		3_prime_UTR_variant	5/5	ENST00000316509.11	NP_055047.2
VAMP2	NM_001330125.1	c.*1590T>C		3_prime_UTR_variant	5/5		NP_001317054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP2	ENST00000316509.11	c.*1590T>C		3_prime_UTR_variant	5/5	1	NM_014232.3	ENSP00000314214	P1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101124 AN: 151100 Hom.: 34080 Cov.: 27

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.786 AC: 33 AN: 42 Hom.: 12 Cov.: 0 AF XY: 0.778 AC XY: 28 AN XY: 36

Gnomad4 FIN exome AF: 0.765

Gnomad4 NFE exome AF: 0.875

GnomAD4 genome AF: 0.669 AC: 101194 AN: 151218 Hom.: 34105 Cov.: 27 AF XY: 0.675 AC XY: 49800 AN XY: 73820

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.649

Alfa AF: 0.664 Hom.: 33273

Bravo AF: 0.658

Asia WGS AF: 0.626 AC: 2177 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1150; hg19: chr17-8062583;