chr5-76179433-T-C

Variant names:

• chr5-76179433-T-C
• rs2055439
• NM_014979.4:c.581-15486T>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.581-15486T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,026 control chromosomes in the GnomAD database, including 28,743 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 0.59 (28743 hom., cov: 32)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.581-15486T>C		intron_variant	Intron 2 of 12	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.581-15486T>C		intron_variant	Intron 2 of 12	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.581-15486T>C		intron_variant	Intron 2 of 12	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90006 AN: 151908 Hom.: 28686 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.593 AC: 90121 AN: 152026 Hom.: 28743 Cov.: 32 AF XY: 0.597 AC XY: 44340 AN XY: 74272

African (AFR) AF: 0.795 AC: 32950 AN: 41470

American (AMR) AF: 0.646 AC: 9873 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3470

East Asian (EAS) AF: 0.913 AC: 4724 AN: 5176

South Asian (SAS) AF: 0.591 AC: 2840 AN: 4808

European-Finnish (FIN) AF: 0.470 AC: 4964 AN: 10552

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31357 AN: 67954

Other (OTH) AF: 0.566 AC: 1196 AN: 2112

Alfa AF: 0.496 Hom.: 9991

Bravo AF: 0.618

Asia WGS AF: 0.757 AC: 2631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.70
PhyloP100		0.074
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: rs2055439; hg19: chr5-75475258; COSMIC: COSV59216534;