rs382571

Positions:

• chr17-43019464-G-A
• chr17-43019464-G-T

Variant summary

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

The NM_006373.4(VAT1):​c.388-665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,138 control chromosomes in the GnomAD database, including 44,263 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 0.76 (44238 hom., cov: 31)
  • Exomes 𝑓: 0.82 (25 hom.)
• Consequence: VAT1 NM_006373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAT1	NM_006373.4	c.388-665C>T		intron_variant		ENST00000355653.8	NP_006364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAT1	ENST00000355653.8	c.388-665C>T		intron_variant		1	NM_006373.4	ENSP00000347872	P1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114961 AN: 151946 Hom.: 44221 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.824 AC: 61 AN: 74 Hom.: 25 Cov.: 0 AF XY: 0.765 AC XY: 26 AN XY: 34

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.756 AC: 115017 AN: 152064 Hom.: 44238 Cov.: 31 AF XY: 0.757 AC XY: 56243 AN XY: 74328

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.781

Alfa AF: 0.796 Hom.: 27133

Bravo AF: 0.761

Asia WGS AF: 0.779 AC: 2706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs382571; hg19: chr17-41171481;