5-76341737-C-T

Variant names:

• chr5-76341737-C-T
• rs246819
• NM_001297716.2:c.2001-11393C>T

Variant summary

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

The NM_001297716.2(SV2C):​c.2001-11393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,864 control chromosomes in the GnomAD database, including 19,367 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 0.47 (19367 hom., cov: 30)
• Consequence: SV2C NM_001297716.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913
• Publications: 5 publications found

Genes affected

SV2C (HGNC:30670): (synaptic vesicle glycoprotein 2C) Predicted to enable transmembrane transporter activity. Predicted to be involved in chemical synaptic transmission; neurotransmitter transport; and transmembrane transport. Predicted to be located in plasma membrane and synaptic vesicle. Predicted to be active in neuron projection and synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302117 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297716.2. 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
	SV2C	NM_001297716.2		c.2001-11393C>T		intron	N/A	NP_001284645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	ENST00000322285.7	TSL:2	c.2001-11393C>T		intron	N/A	ENSP00000316983.7
	ENSG00000302117	ENST00000784489.1		n.63-212C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71878 AN: 151744 Hom.: 19352 Cov.: 30

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.474 AC: 71917 AN: 151864 Hom.: 19367 Cov.: 30 AF XY: 0.476 AC XY: 35360 AN XY: 74212

African (AFR) AF: 0.211 AC: 8755 AN: 41398

American (AMR) AF: 0.553 AC: 8443 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1855 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4307 AN: 5158

South Asian (SAS) AF: 0.569 AC: 2730 AN: 4794

European-Finnish (FIN) AF: 0.517 AC: 5455 AN: 10544

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38671 AN: 67930

Other (OTH) AF: 0.510 AC: 1077 AN: 2110

Alfa AF: 0.547 Hom.: 32844

Bravo AF: 0.471

Asia WGS AF: 0.682 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.2
DANN	Benign	0.57
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs246819; hg19: chr5-75637562; COSMIC: COSV59217057;