rs6453204

Positions:

• chr5-76143375-A-G
• chr5-76143375-A-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+11045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,122 control chromosomes in the GnomAD database, including 61,586 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 0.90 (61586 hom., cov: 30)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2C	NM_014979.4	c.580+11045A>G		intron_variant		ENST00000502798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2C	ENST00000502798.7	c.580+11045A>G		intron_variant		1	NM_014979.4	P1
SV2C	ENST00000322285.7	c.580+11045A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136695 AN: 152004 Hom.: 61536 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.899 AC: 136797 AN: 152122 Hom.: 61586 Cov.: 30 AF XY: 0.898 AC XY: 66756 AN XY: 74378

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.891

Alfa AF: 0.916 Hom.: 12558

Bravo AF: 0.887

Asia WGS AF: 0.880 AC: 3062 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	0.89
DANN	Benign	0.14

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: rs6453204; hg19: chr5-75439200;