rs10514058

Positions:

• chr5-76126861-G-A
• chr5-76126861-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000502798.7(SV2C):​c.-101-4789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 152,244 control chromosomes in the GnomAD database, including 46 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 0.020 (46 hom., cov: 32)
• Consequence: SV2C ENST00000502798.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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=-0.92).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0201 (3067/152244) while in subpopulation SAS AF= 0.044 (212/4814). AF 95% confidence interval is 0.0392. There are 46 homozygotes in gnomad4. There are 1516 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SV2C	NM_014979.4	c.-101-4789G>A		intron_variant		ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.-101-4789G>A		intron_variant		1	NM_014979.4	ENSP00000423541	P1
SV2C	ENST00000322285.7	c.-101-4789G>A		intron_variant		2		ENSP00000316983

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3075 AN: 152128 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.00422

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0201 AC: 3067 AN: 152244 Hom.: 46 Cov.: 32 AF XY: 0.0204 AC XY: 1516 AN XY: 74438

Gnomad4 AFR AF: 0.00421

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00961 Hom.: 4

Bravo AF: 0.0183

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.55

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: rs10514058; hg19: chr5-75422686;