rs12522618

Positions:

• chr5-76160114-G-A
• chr5-76160114-G-C
• chr5-76160114-G-T

Variant summary

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

The NM_014979.4(SV2C):​c.580+27784G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,892 control chromosomes in the GnomAD database, including 33,930 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 0.66 (33930 hom., cov: 32)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2C	NM_014979.4	c.580+27784G>A		intron_variant		ENST00000502798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2C	ENST00000502798.7	c.580+27784G>A		intron_variant		1	NM_014979.4	P1
SV2C	ENST00000322285.7	c.580+27784G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100028 AN: 151776 Hom.: 33869 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.659 AC: 100146 AN: 151892 Hom.: 33930 Cov.: 32 AF XY: 0.662 AC XY: 49151 AN XY: 74248

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.654

Alfa AF: 0.626 Hom.: 5590

Bravo AF: 0.678

Asia WGS AF: 0.813 AC: 2819 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.12

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: rs12522618; hg19: chr5-75455939;