2-85567174-T-C

Variant names:

• chr2-85567174-T-C
• rs10187424
• ENST00000432071.1:c.-76+5530T>C

Variant summary

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

The ENST00000432071.1(VAMP8):​c.-76+5530T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 147,202 control chromosomes in the GnomAD database, including 17,129 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 0.48 (17129 hom., cov: 26)
• Consequence: VAMP8 ENST00000432071.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 108 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432071.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP8	ENST00000432071.1	TSL:3	c.-76+5530T>C		intron	N/A	ENSP00000407984.1	C9JXZ5

Frequencies

GnomAD3 genomes AF: 0.479 AC: 70420 AN: 147082 Hom.: 17094 Cov.: 26

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.479 AC: 70513 AN: 147202 Hom.: 17129 Cov.: 26 AF XY: 0.476 AC XY: 34233 AN XY: 71916

African (AFR) AF: 0.643 AC: 25718 AN: 39974

American (AMR) AF: 0.386 AC: 5729 AN: 14836

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1231 AN: 3308

East Asian (EAS) AF: 0.397 AC: 1959 AN: 4932

South Asian (SAS) AF: 0.389 AC: 1760 AN: 4522

European-Finnish (FIN) AF: 0.440 AC: 4513 AN: 10258

Middle Eastern (MID) AF: 0.377 AC: 107 AN: 284

European-Non Finnish (NFE) AF: 0.426 AC: 28146 AN: 66132

Other (OTH) AF: 0.456 AC: 934 AN: 2048

Alfa AF: 0.432 Hom.: 47384

Bravo AF: 0.481

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.32
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10187424; hg19: chr2-85794297;