rs4704296

Positions:

• chr5-76206585-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.762-3151G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,088 control chromosomes in the GnomAD database, including 31,176 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 0.63 (31176 hom., cov: 32)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2C	NM_014979.4	c.762-3151G>C		intron_variant		ENST00000502798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2C	ENST00000502798.7	c.762-3151G>C		intron_variant		1	NM_014979.4	P1
SV2C	ENST00000322285.7	c.762-3151G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95927 AN: 151970 Hom.: 31114 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.632 AC: 96051 AN: 152088 Hom.: 31176 Cov.: 32 AF XY: 0.638 AC XY: 47414 AN XY: 74340

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.634

Alfa AF: 0.585 Hom.: 3300

Bravo AF: 0.649

Asia WGS AF: 0.810 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.31

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: rs4704296; hg19: chr5-75502410;