NM_001323032.3:c.-391-51751C>T

Variant names:

• chr15-91174122-C-T
• rs886144
• NM_001323032.3:c.-391-51751C>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.-391-51751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,042 control chromosomes in the GnomAD database, including 10,513 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 0.35 (10513 hom., cov: 33)
• Consequence: SV2B NM_001323032.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 11 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2B	NM_001323032.3	c.-391-51751C>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.-391-51751C>T		intron_variant	Intron 1 of 12	5	NM_001323032.3	ENSP00000377779.1
SV2B	ENST00000557410.5	n.-392+45312C>T		intron_variant	Intron 2 of 14	1		ENSP00000450992.1
SV2B	ENST00000545111.6	c.-3+73759C>T		intron_variant	Intron 1 of 11	2		ENSP00000443243.2
SV2B	ENST00000557291.1	n.493+71802C>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53755 AN: 151926 Hom.: 10509 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.354 AC: 53791 AN: 152042 Hom.: 10513 Cov.: 33 AF XY: 0.344 AC XY: 25544 AN XY: 74304

African (AFR) AF: 0.480 AC: 19901 AN: 41452

American (AMR) AF: 0.257 AC: 3916 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1574 AN: 3472

East Asian (EAS) AF: 0.0595 AC: 308 AN: 5178

South Asian (SAS) AF: 0.249 AC: 1199 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2838 AN: 10556

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22810 AN: 67982

Other (OTH) AF: 0.357 AC: 755 AN: 2114

Alfa AF: 0.333 Hom.: 25781

Bravo AF: 0.361

Asia WGS AF: 0.173 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.68
DANN	Benign	0.58
PhyloP100		-1.1
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: rs886144; hg19: chr15-91717352; COSMIC: COSV67766176;