2-85561615-C-A

Position:

• chr2-85561615-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000432071.1(VAMP8):​c.-105C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 585,082 control chromosomes in the GnomAD database, including 10,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2439 hom., cov: 33)
  • Exomes 𝑓: 0.18 (8336 hom.)
• Consequence: VAMP8 ENST00000432071.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.608

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-85561615-C-A is Benign according to our data. Variant chr2-85561615-C-A is described in ClinVar as [Benign]. Clinvar id is 1289081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.85561615C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP8	ENST00000432071.1	c.-105C>A		5_prime_UTR_variant	1/3	3		ENSP00000407984.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24229 AN: 152146 Hom.: 2438 Cov.: 33

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.183 AC: 79165 AN: 432818 Hom.: 8336 Cov.: 4 AF XY: 0.178 AC XY: 40322 AN XY: 226312

Gnomad4 AFR exome AF: 0.0512

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0167

Gnomad4 SAS exome AF: 0.0789

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.159 AC: 24236 AN: 152264 Hom.: 2439 Cov.: 33 AF XY: 0.157 AC XY: 11717 AN XY: 74460

Gnomad4 AFR AF: 0.0534

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.170

Alfa AF: 0.199 Hom.: 738

Bravo AF: 0.148

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115669754; hg19: chr2-85788738; COSMIC: COSV52090633; COSMIC: COSV52090633;