dbSNP rs3731828: VAMP8:p.Asn46Asn (chr2-85579143-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003761.5(VAMP8):c.138C>T(p.Asn46Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,603,078 control chromosomes in the GnomAD database, including 61,693 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 0.30 ( 6887 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54806 hom. )

Consequence

VAMP8
NM_003761.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

40 publications found

Variant links:

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]

VAMP8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=1.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAMP8	NM_003761.5 link	c.138C>T	p.Asn46Asn	synonymous_variant	Exon 2 of 3	ENST00000263864.10	NP_003752.2
VAMP8	XM_017005170.2 link	c.138C>T	p.Asn46Asn	synonymous_variant	Exon 2 of 4		XP_016860659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
VAMP8	ENST00000263864.10 link	c.138C>T	p.Asn46Asn	synonymous_variant	Exon 2 of 3	1	NM_003761.5	ENSP00000263864.5
VAMP8	ENST00000409760.1 link	c.138C>T	p.Asn46Asn	synonymous_variant	Exon 2 of 4	3		ENSP00000387094.1
VAMP8	ENST00000432071.1 link	c.60C>T	p.Asn20Asn	synonymous_variant	Exon 2 of 3	3		ENSP00000407984.1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44885

AN:

151848

Hom.:

6875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.272

GnomAD2 exomes

AF:

0.256

AC:

60922

AN:

238188

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.362

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.272

AC:

395057

AN:

1451112

Hom.:

54806

Cov.:

AF XY:

0.269

AC XY:

193975

AN XY:

720456

show subpopulations

African (AFR)

AF:

0.358

AC:

11934

AN:

33322

American (AMR)

AF:

0.191

AC:

8377

AN:

43806

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6153

AN:

25806

East Asian (EAS)

AF:

0.313

AC:

12314

AN:

39330

South Asian (SAS)

AF:

0.163

AC:

13877

AN:

85002

European-Finnish (FIN)

AF:

0.299

AC:

15813

AN:

52862

Middle Eastern (MID)

AF:

0.212

AC:

1217

AN:

5734

European-Non Finnish (NFE)

AF:

0.280

AC:

309136

AN:

1105326

Other (OTH)

AF:

0.271

AC:

16236

AN:

59924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

14500

29000

43500

58000

72500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10388

20776

31164

41552

51940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.296

AC:

44921

AN:

151966

Hom.:

6887

Cov.:

AF XY:

0.294

AC XY:

21810

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.364

AC:

15076

AN:

41420

American (AMR)

AF:

0.220

AC:

3360

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

763

AN:

3468

East Asian (EAS)

AF:

0.326

AC:

1680

AN:

5154

South Asian (SAS)

AF:

0.163

AC:

788

AN:

4820

European-Finnish (FIN)

AF:

0.320

AC:

3386

AN:

10568

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.278

AC:

18898

AN:

67964

Other (OTH)

AF:

0.277

AC:

583

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1614

3228

4841

6455

8069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.274

Hom.:

13802

Bravo

AF:

0.295

Asia WGS

AF:

0.279

AC:

968

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over