rs2597909

Positions:

• chr15-91118489-C-T

Variant summary

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

The NM_001323032.3(SV2B):​c.-392+18126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,246 control chromosomes in the GnomAD database, including 1,052 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 0.11 (1052 hom., cov: 32)
• Consequence: SV2B NM_001323032.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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]

SV2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SV2B	NM_001323032.3	c.-392+18126C>T		intron_variant		ENST00000394232.6	NP_001309961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SV2B	ENST00000394232.6	c.-392+18126C>T		intron_variant		5	NM_001323032.3	ENSP00000377779.1
SV2B	ENST00000557410.5	n.-479-10234C>T		intron_variant		1		ENSP00000450992.1
SV2B	ENST00000545111.6	c.-3+18126C>T		intron_variant		2		ENSP00000443243.2
SV2B	ENST00000557291.1	n.493+16169C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16639 AN: 152128 Hom.: 1055 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.109 AC: 16645 AN: 152246 Hom.: 1052 Cov.: 32 AF XY: 0.111 AC XY: 8232 AN XY: 74434

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0865

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.0927

Alfa AF: 0.0861 Hom.: 768

Bravo AF: 0.111

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.47

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: rs2597909; hg19: chr15-91661719;