chr17-43019464-G-A

Variant names:

• chr17-43019464-G-A
• rs382571
• NM_006373.4:c.388-665C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006373.4. 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
	VAT1	NM_006373.4	MANE Select	c.388-665C>T		intron	N/A	NP_006364.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAT1	ENST00000355653.8	TSL:1 MANE Select	c.388-665C>T		intron	N/A	ENSP00000347872.2
	VAT1	ENST00000589709.1	TSL:4	c.-26C>T		5_prime_UTR	Exon 1 of 4	ENSP00000467131.1
	VAT1	ENST00000587173.5	TSL:2	c.184-665C>T		intron	N/A	ENSP00000465946.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.809 AC: 55 AN: 68

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.612 AC: 25347 AN: 41446

American (AMR) AF: 0.835 AC: 12746 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2857 AN: 3466

East Asian (EAS) AF: 0.914 AC: 4736 AN: 5180

South Asian (SAS) AF: 0.732 AC: 3535 AN: 4830

European-Finnish (FIN) AF: 0.762 AC: 8043 AN: 10562

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55166 AN: 67994

Other (OTH) AF: 0.781 AC: 1650 AN: 2112

Alfa AF: 0.803 Hom.: 45518

Bravo AF: 0.761

Asia WGS AF: 0.779 AC: 2706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.85
PhyloP100		-0.066
PromoterAI		0.018	Neutral
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: rs382571; hg19: chr17-41171481;