rs8027498

Variant names:

• chr15-91251404-G-A
• rs8027498
• NM_001323032.3:c.452-415G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000301795 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323032.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2B	NM_001323032.3	MANE Select	c.452-415G>A		intron	N/A	NP_001309961.1
	SV2B	NM_001323031.2		c.452-415G>A		intron	N/A	NP_001309960.1
	SV2B	NM_001323037.3		c.452-415G>A		intron	N/A	NP_001309966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2B	ENST00000394232.6	TSL:5 MANE Select	c.452-415G>A		intron	N/A	ENSP00000377779.1
	SV2B	ENST00000330276.4	TSL:1	c.452-415G>A		intron	N/A	ENSP00000332818.4
	SV2B	ENST00000557410.5	TSL:1	n.452-415G>A		intron	N/A	ENSP00000450992.1

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

African (AFR) AF: 0.452 AC: 18747 AN: 41494

American (AMR) AF: 0.210 AC: 3203 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3468

East Asian (EAS) AF: 0.151 AC: 784 AN: 5176

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4818

European-Finnish (FIN) AF: 0.185 AC: 1963 AN: 10584

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16830 AN: 67978

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.270 Hom.: 12619

Bravo AF: 0.305

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.039
DANN	Benign	0.38
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8027498; hg19: chr15-91794634;