5-76316507-T-G

Variant names:

• chr5-76316507-T-G
• rs2913257
• NM_014979.4:c.2001-8857T>G

Variant summary

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

The NM_014979.4(SV2C):​c.2001-8857T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 152,260 control chromosomes in the GnomAD database, including 705 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 0.092 (705 hom., cov: 32)
• Consequence: SV2C NM_014979.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• 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]

SV2C-AS2 (HGNC:58251):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	NM_014979.4	MANE Select	c.2001-8857T>G		intron	N/A	NP_055794.3	Q496J9
	SV2C	NM_001297716.2		c.2000+14962T>G		intron	N/A	NP_001284645.1	B3KT41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	ENST00000502798.7	TSL:1 MANE Select	c.2001-8857T>G		intron	N/A	ENSP00000423541.2	Q496J9
	SV2C	ENST00000322285.7	TSL:2	c.2000+14962T>G		intron	N/A	ENSP00000316983.7	B3KT41
	SV2C-AS2	ENST00000502589.2	TSL:5	n.532-5045A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13995 AN: 152142 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0834

Gnomad OTH AF: 0.0936

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

GnomAD4 genome AF: 0.0920 AC: 14012 AN: 152260 Hom.: 705 Cov.: 32 AF XY: 0.0944 AC XY: 7028 AN XY: 74442

African (AFR) AF: 0.0839 AC: 3488 AN: 41550

American (AMR) AF: 0.140 AC: 2148 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3472

East Asian (EAS) AF: 0.114 AC: 588 AN: 5178

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1268 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0833 AC: 5668 AN: 68030

Other (OTH) AF: 0.0926 AC: 196 AN: 2116

Alfa AF: 0.0795 Hom.: 417

Bravo AF: 0.0944

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.26
PhyloP100		0.13
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: rs2913257; hg19: chr5-75612332;