rs258619

Variant names:

• chr5-76097465-G-C
• rs258619
• NM_014979.4:c.-102+13953G>C

Variant summary

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

The NM_014979.4(SV2C):​c.-102+13953G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,096 control chromosomes in the GnomAD database, including 3,199 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 0.18 (3199 hom., cov: 33)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.-102+13953G>C		intron_variant	Intron 1 of 12	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.-102+13953G>C		intron_variant	Intron 1 of 12	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.-102+13953G>C		intron_variant	Intron 1 of 12	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27872 AN: 151978 Hom.: 3192 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0968

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.183 AC: 27888 AN: 152096 Hom.: 3199 Cov.: 33 AF XY: 0.184 AC XY: 13701 AN XY: 74342

African (AFR) AF: 0.0499 AC: 2071 AN: 41528

American (AMR) AF: 0.179 AC: 2738 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5170

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4812

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10560

Middle Eastern (MID) AF: 0.0938 AC: 27 AN: 288

European-Non Finnish (NFE) AF: 0.245 AC: 16620 AN: 67970

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.207 Hom.: 434

Bravo AF: 0.171

Asia WGS AF: 0.277 AC: 961 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		0.061
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs258619; hg19: chr5-75393290; COSMIC: COSV59216375;