rs258619

Positions:

• chr5-76097465-G-C

Variant summary

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

The NM_014979.4(SV2C):​c.-102+13953G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,096 control chromosomes in the GnomAD database, including 3,199 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 0.18 (3199 hom., cov: 33)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SV2C	NM_014979.4	c.-102+13953G>C		intron_variant		ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.-102+13953G>C		intron_variant		1	NM_014979.4	ENSP00000423541	P1
SV2C	ENST00000322285.7	c.-102+13953G>C		intron_variant		2		ENSP00000316983

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27872 AN: 151978 Hom.: 3192 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0968

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.183 AC: 27888 AN: 152096 Hom.: 3199 Cov.: 33 AF XY: 0.184 AC XY: 13701 AN XY: 74342

Gnomad4 AFR AF: 0.0499

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.179

Alfa AF: 0.207 Hom.: 434

Bravo AF: 0.171

Asia WGS AF: 0.277 AC: 961 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.82

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: rs258619; hg19: chr5-75393290; COSMIC: COSV59216375;