2-85589211-A-G

Position:

• chr2-85589211-A-G

Variant summary

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

The NM_006634.3(VAMP5):​c.4-2514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,262 control chromosomes in the GnomAD database, including 49,550 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 0.80 (49550 hom., cov: 32)
• Consequence: VAMP5 NM_006634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13

Genes affected

VAMP5 (HGNC:12646): (vesicle associated membrane protein 5) Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein are the main components of a protein complex involved in the docking and/or fusion of vesicles and cell membranes. The VAMP5 gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family and the SNARE superfamily. This VAMP family member may participate in vesicle trafficking events that are associated with myogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP5	NM_006634.3	c.4-2514A>G		intron_variant		ENST00000306384.5	NP_006625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP5	ENST00000306384.5	c.4-2514A>G		intron_variant		1	NM_006634.3	ENSP00000305647	P1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121606 AN: 152144 Hom.: 49499 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.752

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.799 AC: 121709 AN: 152262 Hom.: 49550 Cov.: 32 AF XY: 0.795 AC XY: 59219 AN XY: 74444

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.751

Alfa AF: 0.769 Hom.: 62719

Bravo AF: 0.789

Asia WGS AF: 0.624 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0030
DANN	Benign	0.40

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: rs1254900; hg19: chr2-85816334;