rs8027498

Positions:

• chr15-91251404-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323032.3(SV2B):​c.452-415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,114 control chromosomes in the GnomAD database, including 7,417 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 (7417 hom., cov: 33)
• Consequence: SV2B NM_001323032.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

SV2B (HGNC:16874): (synaptic vesicle glycoprotein 2B) This gene encodes a member of the synaptic vesicle proteins 2 (SV2) family and major facilitator superfamily of proteins. This protein and other members of the family are localized to synaptic vesicles and may function in the regulation of vesicle trafficking and exocytosis. Studies in mice suggest that the encoded protein may act as a protein receptor for botulinum neurotoxin E in neurons, and that this protein may be important for the integrity of the glomerular filtration barrier. This gene shows reduced expression in areas of synaptic loss in the hippocampus of human temporal lobe epilepsy patients. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2B	NM_001323032.3	c.452-415G>A		intron_variant		ENST00000394232.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2B	ENST00000394232.6	c.452-415G>A		intron_variant		5	NM_001323032.3	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44881 AN: 151996 Hom.: 7395 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44941 AN: 152114 Hom.: 7417 Cov.: 33 AF XY: 0.289 AC XY: 21480 AN XY: 74370

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.301

Alfa AF: 0.259 Hom.: 5827

Bravo AF: 0.305

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.039
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs8027498; hg19: chr15-91794634;