rs1010

chr2-85581859-T-Cchr2-85581859-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003761.5(VAMP8):c.*143T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,133,830 control chromosomes in the GnomAD database, including 95,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15903 hom., cov: 30)
  • Exomes 𝑓: 0.40 (80065 hom.)
• Consequence: VAMP8 NM_003761.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0580

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-85581859-T-C is Benign according to our data. Variant chr2-85581859-T-C is described in ClinVar as [Benign]. Clinvar id is 1182311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAMP8	NM_003761.5	c.*143T>C		3_prime_UTR_variant	3/3	ENST00000263864.10
VAMP8	XM_017005170.2	c.*279T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAMP8	ENST00000263864.10	c.*143T>C		3_prime_UTR_variant	3/3	1	NM_003761.5	P1
VAMP8	ENST00000409760.1	c.*279T>C		3_prime_UTR_variant	4/4	3
VAMP8	ENST00000432071.1	c.*143T>C		3_prime_UTR_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68489 AN: 151694 Hom.: 15880 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.402 AC: 395243 AN: 982016 Hom.: 80065 Cov.: 13 AF XY: 0.403 AC XY: 200056 AN XY: 496772

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.452 AC: 68561 AN: 151814 Hom.: 15903 Cov.: 30 AF XY: 0.450 AC XY: 33391 AN XY: 74186

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.435

Alfa AF: 0.413 Hom.: 14248

Bravo AF: 0.452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2020

This variant is associated with the following publications: (PMID: 25691096) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.5
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1010; hg19: chr2-85808982; COSMIC: COSV55705317; COSMIC: COSV55705317;