chr2-85587861-C-T

Variant names:

• chr2-85587861-C-T
• rs10206961
• NM_006634.3:c.3+3368C>T

Variant summary

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

The NM_006634.3(VAMP5):​c.3+3368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,026 control chromosomes in the GnomAD database, including 23,718 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 0.52 (23718 hom., cov: 32)
• Consequence: VAMP5 NM_006634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 17 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 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.3+3368C>T		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.3+3368C>T		intron	N/A	ENSP00000305647.4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79347 AN: 151908 Hom.: 23673 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.523 AC: 79446 AN: 152026 Hom.: 23718 Cov.: 32 AF XY: 0.517 AC XY: 38394 AN XY: 74300

African (AFR) AF: 0.834 AC: 34604 AN: 41506

American (AMR) AF: 0.410 AC: 6254 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1211 AN: 3462

East Asian (EAS) AF: 0.382 AC: 1979 AN: 5174

South Asian (SAS) AF: 0.385 AC: 1848 AN: 4806

European-Finnish (FIN) AF: 0.382 AC: 4027 AN: 10552

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28127 AN: 67950

Other (OTH) AF: 0.486 AC: 1028 AN: 2114

Alfa AF: 0.438 Hom.: 31055

Bravo AF: 0.536

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.77
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10206961; hg19: chr2-85814984;