5-75995992-A-G

Variant names:

• chr5-75995992-A-G
• rs12657643
• XM_011543282.4:c.-101-135658A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011543282.4(SV2C):​c.-101-135658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,146 control chromosomes in the GnomAD database, including 3,924 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 0.21 (3924 hom., cov: 32)
• Consequence: SV2C XM_011543282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	XM_011543282.4	c.-101-135658A>G		intron_variant	Intron 1 of 12		XP_011541584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31342 AN: 152028 Hom.: 3913 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.206 AC: 31377 AN: 152146 Hom.: 3924 Cov.: 32 AF XY: 0.214 AC XY: 15887 AN XY: 74384

African (AFR) AF: 0.229 AC: 9520 AN: 41520

American (AMR) AF: 0.290 AC: 4433 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.614 AC: 3158 AN: 5144

South Asian (SAS) AF: 0.276 AC: 1330 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1992 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9722 AN: 67994

Other (OTH) AF: 0.235 AC: 496 AN: 2114

Alfa AF: 0.162 Hom.: 4470

Bravo AF: 0.219

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.57
PhyloP100		-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12657643; hg19: chr5-75291817;