rs4374745

Variant names:

• chr5-76019502-C-T
• rs4374745
• XM_011543282.4:c.-101-112148C>T

Variant summary

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

The XM_011543282.4(SV2C):​c.-101-112148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,950 control chromosomes in the GnomAD database, including 28,719 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 0.61 (28719 hom., cov: 32)
• Consequence: SV2C XM_011543282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	XM_011543282.4	c.-101-112148C>T		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: 0.607 AC: 92176 AN: 151832 Hom.: 28684 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.607 AC: 92259 AN: 151950 Hom.: 28719 Cov.: 32 AF XY: 0.602 AC XY: 44676 AN XY: 74242

African (AFR) AF: 0.717 AC: 29717 AN: 41444

American (AMR) AF: 0.528 AC: 8056 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2039 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1508 AN: 5152

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4806

European-Finnish (FIN) AF: 0.629 AC: 6636 AN: 10558

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.596 AC: 40464 AN: 67944

Other (OTH) AF: 0.595 AC: 1252 AN: 2104

Alfa AF: 0.592 Hom.: 43829

Bravo AF: 0.605

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.062
DANN	Benign	0.53
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs4374745; hg19: chr5-75315327;