chr15-91200629-G-T

Variant names:

• chr15-91200629-G-T
• rs8039294
• NM_001323032.3:c.-391-25244G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323032.3(SV2B):​c.-391-25244G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,088 control chromosomes in the GnomAD database, including 6,567 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 0.21 (6567 hom., cov: 32)
• Consequence: SV2B NM_001323032.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2B	NM_001323032.3	c.-391-25244G>T		intron_variant	Intron 1 of 12	ENST00000394232.6	NP_001309961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2B	ENST00000394232.6	c.-391-25244G>T		intron_variant	Intron 1 of 12	5	NM_001323032.3	ENSP00000377779.1
SV2B	ENST00000557410.5	n.-391-25244G>T		intron_variant	Intron 2 of 14	1		ENSP00000450992.1
SV2B	ENST00000545111.6	c.-2-51190G>T		intron_variant	Intron 1 of 11	2		ENSP00000443243.2
SV2B	ENST00000557291.1	n.494-51190G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32591 AN: 151970 Hom.: 6556 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.215 AC: 32646 AN: 152088 Hom.: 6567 Cov.: 32 AF XY: 0.208 AC XY: 15494 AN XY: 74356

African (AFR) AF: 0.534 AC: 22116 AN: 41446

American (AMR) AF: 0.114 AC: 1739 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0701 AC: 338 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1118 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6440 AN: 67998

Other (OTH) AF: 0.185 AC: 390 AN: 2108

Alfa AF: 0.0801 Hom.: 183

Bravo AF: 0.232

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.071
DANN	Benign	0.75
PhyloP100		-2.0
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: rs8039294; hg19: chr15-91743859;