ENST00000432071.1:c.-76+5530T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAMP8	ENST00000432071.1	c.-76+5530T>C		intron_variant	Intron 1 of 2	3		ENSP00000407984.1

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.456

Alfa AF: 0.417 Hom.: 28867

Bravo AF: 0.481

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10187424; hg19: chr2-85794297;