rs4703699

Variant names:

• chr5-76210125-G-A
• rs4703699
• NM_014979.4:c.913+238G>A

Variant summary

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

The NM_014979.4(SV2C):​c.913+238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 152,368 control chromosomes in the GnomAD database, including 74,351 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 0.99 (74351 hom., cov: 33)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.913+238G>A		intron_variant	Intron 4 of 12	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.913+238G>A		intron_variant	Intron 4 of 12	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.913+238G>A		intron_variant	Intron 4 of 12	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150397 AN: 152250 Hom.: 74292 Cov.: 33

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.987

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.990

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

GnomAD4 genome AF: 0.988 AC: 150515 AN: 152368 Hom.: 74351 Cov.: 33 AF XY: 0.989 AC XY: 73673 AN XY: 74506

African (AFR) AF: 0.996 AC: 41387 AN: 41574

American (AMR) AF: 0.991 AC: 15172 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.999 AC: 4821 AN: 4828

European-Finnish (FIN) AF: 0.987 AC: 10488 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.980 AC: 66697 AN: 68046

Other (OTH) AF: 0.990 AC: 2095 AN: 2116

Alfa AF: 0.986 Hom.: 9324

Bravo AF: 0.989

Asia WGS AF: 0.999 AC: 3473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.23
PhyloP100		-1.4
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: rs4703699; hg19: chr5-75505950;