2-85591365-T-C

Variant names:

• chr2-85591365-T-C
• rs719023
• NM_006634.3:c.4-360T>C

Variant summary

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

The NM_006634.3(VAMP5):​c.4-360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,068 control chromosomes in the GnomAD database, including 22,809 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 0.54 (22809 hom., cov: 32)
• Consequence: VAMP5 NM_006634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006634.3. 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
	VAMP5	NM_006634.3	MANE Select	c.4-360T>C		intron	N/A	NP_006625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP5	ENST00000306384.5	TSL:1 MANE Select	c.4-360T>C		intron	N/A	ENSP00000305647.4
	VAMP5	ENST00000462451.1	TSL:2	n.-232T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81584 AN: 151950 Hom.: 22809 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.537 AC: 81609 AN: 152068 Hom.: 22809 Cov.: 32 AF XY: 0.533 AC XY: 39615 AN XY: 74342

African (AFR) AF: 0.469 AC: 19451 AN: 41466

American (AMR) AF: 0.454 AC: 6942 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2116 AN: 3468

East Asian (EAS) AF: 0.131 AC: 676 AN: 5166

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4822

European-Finnish (FIN) AF: 0.660 AC: 6978 AN: 10576

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41468 AN: 67976

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

Alfa AF: 0.575 Hom.: 50772

Bravo AF: 0.516

Asia WGS AF: 0.277 AC: 969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs719023; hg19: chr2-85818488;