17-43024671-T-C

Position:

• chr17-43024671-T-C

Variant summary

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

The ENST00000590924.5(VAT1):​c.-16+318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,982 control chromosomes in the GnomAD database, including 7,701 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 0.31 (7701 hom., cov: 30)
• Consequence: VAT1 ENST00000590924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

Genes affected

VAT1 (HGNC:16919): (vesicle amine transport 1) Synaptic vesicles are responsible for regulating the storage and release of neurotransmitters in the nerve terminal. The protein encoded by this gene is an abundant integral membrane protein of cholinergic synaptic vesicles and is thought to be involved in vesicular transport. It belongs to the quinone oxidoreductase subfamily of zinc-containing alcohol dehydrogenase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAT1	ENST00000587062.1	c.-29+318A>G		intron_variant		4		ENSP00000468401
VAT1	ENST00000590924.5	c.-16+318A>G		intron_variant		3		ENSP00000466322

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47146 AN: 151862 Hom.: 7698 Cov.: 30

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.310 AC: 47168 AN: 151982 Hom.: 7701 Cov.: 30 AF XY: 0.316 AC XY: 23442 AN XY: 74270

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.331

Alfa AF: 0.321 Hom.: 7938

Bravo AF: 0.292

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298862; hg19: chr17-41176688;