5-76274833-A-G

Variant names:

• chr5-76274833-A-G
• rs1995381
• NM_014979.4:c.914-10329A>G

Variant summary

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

The ENST00000502798.7(SV2C):​c.914-10329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,114 control chromosomes in the GnomAD database, including 2,129 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 0.14 (2129 hom., cov: 31)
• Consequence: SV2C ENST00000502798.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502798.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	NM_014979.4	MANE Select	c.914-10329A>G		intron	N/A	NP_055794.3
	SV2C	NM_001297716.2		c.914-10329A>G		intron	N/A	NP_001284645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	ENST00000502798.7	TSL:1 MANE Select	c.914-10329A>G		intron	N/A	ENSP00000423541.2
	SV2C	ENST00000322285.7	TSL:2	c.914-10329A>G		intron	N/A	ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21907 AN: 151996 Hom.: 2110 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.144 AC: 21965 AN: 152114 Hom.: 2129 Cov.: 31 AF XY: 0.145 AC XY: 10817 AN XY: 74364

African (AFR) AF: 0.270 AC: 11216 AN: 41470

American (AMR) AF: 0.166 AC: 2530 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3472

East Asian (EAS) AF: 0.0994 AC: 514 AN: 5172

South Asian (SAS) AF: 0.0409 AC: 197 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1231 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5549 AN: 68020

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.105 Hom.: 2032

Bravo AF: 0.154

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.075
DANN	Benign	0.50
PhyloP100		-0.98
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: rs1995381; hg19: chr5-75570658;