chr5-76132110-G-A

Variant names:

• chr5-76132110-G-A
• rs10070440
• NM_014979.4:c.360G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_014979.4(SV2C):​c.360G>A​(p.Arg120Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,613,672 control chromosomes in the GnomAD database, including 417,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (29420 hom., cov: 31)
  • Exomes 𝑓: 0.72 (388004 hom.)
• Consequence: SV2C NM_014979.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.26

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-76132110-G-A is Benign according to our data. Variant chr5-76132110-G-A is described in ClinVar as [Benign]. Clinvar id is 3060767.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-4.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.360G>A	p.Arg120Arg	synonymous_variant	Exon 2 of 13	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.360G>A	p.Arg120Arg	synonymous_variant	Exon 2 of 13	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.360G>A	p.Arg120Arg	synonymous_variant	Exon 2 of 13	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89760 AN: 151872 Hom.: 29417 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.597

GnomAD2 exomes AF: 0.626 AC: 155839 AN: 248990 AF XY: 0.645

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.736

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.686

Gnomad NFE exome AF: 0.754

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.719 AC: 1051093 AN: 1461682 Hom.: 388004 Cov.: 76 AF XY: 0.720 AC XY: 523693 AN XY: 727120

Gnomad4 AFR exome AF: 0.309 AC: 10340 AN: 33476

Gnomad4 AMR exome AF: 0.405 AC: 18121 AN: 44720

Gnomad4 ASJ exome AF: 0.739 AC: 19297 AN: 26124

Gnomad4 EAS exome AF: 0.346 AC: 13722 AN: 39682

Gnomad4 SAS exome AF: 0.665 AC: 57310 AN: 86242

Gnomad4 FIN exome AF: 0.696 AC: 37146 AN: 53402

Gnomad4 NFE exome AF: 0.765 AC: 850241 AN: 1111882

Gnomad4 Remaining exome AF: 0.681 AC: 41152 AN: 60390

GnomAD4 genome AF: 0.591 AC: 89781 AN: 151990 Hom.: 29420 Cov.: 31 AF XY: 0.585 AC XY: 43425 AN XY: 74292

Gnomad4 AFR AF: 0.330 AC: 0.329602 AN: 0.329602

Gnomad4 AMR AF: 0.502 AC: 0.502226 AN: 0.502226

Gnomad4 ASJ AF: 0.747 AC: 0.746686 AN: 0.746686

Gnomad4 EAS AF: 0.335 AC: 0.335278 AN: 0.335278

Gnomad4 SAS AF: 0.658 AC: 0.657938 AN: 0.657938

Gnomad4 FIN AF: 0.677 AC: 0.676927 AN: 0.676927

Gnomad4 NFE AF: 0.760 AC: 0.760181 AN: 0.760181

Gnomad4 OTH AF: 0.600 AC: 0.6 AN: 0.6

Alfa AF: 0.673 Hom.: 70409

Bravo AF: 0.558

Asia WGS AF: 0.490 AC: 1706 AN: 3476

EpiCase AF: 0.745

EpiControl AF: 0.753

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SV2C-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.67
Mutation Taster		=98/2	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

Publications

LitVar

Other links and lift over

dbSNP: rs10070440; hg19: chr5-75427935; COSMIC: COSV59220208;