dbSNP rs1058588: VAMP8:c.*32C>T (chr2-85581748-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003761.5(VAMP8):c.*32C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,612,360 control chromosomes in the GnomAD database, including 140,627 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 0.43 ( 14004 hom., cov: 31)

Exomes 𝑓: 0.42 ( 126623 hom. )

Consequence

VAMP8
NM_003761.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.156

Publications

57 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAMP8	NM_003761.5 link	c.*32C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000263864.10	NP_003752.2
VAMP8	XM_017005170.2 link	c.*168C>T		3_prime_UTR_variant	Exon 4 of 4		XP_016860659.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
VAMP8	ENST00000263864.10 link	c.*32C>T	3_prime_UTR_variant	Exon 3 of 3	1	NM_003761.5	ENSP00000263864.5
VAMP8	ENST00000409760.1 link	c.*168C>T	3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000387094.1
VAMP8	ENST00000432071.1 link	c.*32C>T	3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000407984.1

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64943

AN:

151886

Hom.:

13988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.418

Gnomad OTH

AF:

0.416

GnomAD2 exomes

AF:

0.398

AC:

99802

AN:

250570

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.293

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.436

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.415

AC:

606161

AN:

1460356

Hom.:

126623

Cov.:

AF XY:

0.415

AC XY:

301285

AN XY:

726534

show subpopulations

African (AFR)

AF:

0.474

AC:

15854

AN:

33418

American (AMR)

AF:

0.303

AC:

13516

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

9644

AN:

26082

East Asian (EAS)

AF:

0.380

AC:

15066

AN:

39676

South Asian (SAS)

AF:

0.377

AC:

32463

AN:

86150

European-Finnish (FIN)

AF:

0.427

AC:

22787

AN:

53326

Middle Eastern (MID)

AF:

0.371

AC:

2140

AN:

5766

European-Non Finnish (NFE)

AF:

0.422

AC:

469364

AN:

1110940

Other (OTH)

AF:

0.420

AC:

25327

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16437

32874

49310

65747

82184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14376

28752

43128

57504

71880

<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:

0.428

AC:

64994

AN:

152004

Hom.:

14004

Cov.:

AF XY:

0.427

AC XY:

31705

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.478

AC:

19791

AN:

41438

American (AMR)

AF:

0.368

AC:

5616

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1255

AN:

3470

East Asian (EAS)

AF:

0.392

AC:

2022

AN:

5160

South Asian (SAS)

AF:

0.379

AC:

1830

AN:

4826

European-Finnish (FIN)

AF:

0.440

AC:

4648

AN:

10564

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.418

AC:

28425

AN:

67948

Other (OTH)

AF:

0.419

AC:

885

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1893

3786

5680

7573

9466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.416

Hom.:

22374

Bravo

AF:

0.425

Asia WGS

AF:

0.421

AC:

1464

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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