5-76132245-C-T

Variant names:

• chr5-76132245-C-T
• rs73130289
• NM_014979.4:c.495C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014979.4(SV2C):​c.495C>T​(p.Asp165Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,613,976 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (32 hom.)
• Consequence: SV2C NM_014979.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.486
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 5-76132245-C-T is Benign according to our data. Variant chr5-76132245-C-T is described in ClinVar as Benign. ClinVar VariationId is 777396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.486 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1829/152132) while in subpopulation AFR AF = 0.0413 (1712/41498). AF 95% confidence interval is 0.0396. There are 32 homozygotes in GnomAd4. There are 863 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

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.495C>T	p.Asp165Asp	synonymous	Exon 2 of 13	NP_055794.3	Q496J9
	SV2C	NM_001297716.2		c.495C>T	p.Asp165Asp	synonymous	Exon 2 of 13	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.495C>T	p.Asp165Asp	synonymous	Exon 2 of 13	ENSP00000423541.2	Q496J9
	SV2C	ENST00000322285.7	TSL:2	c.495C>T	p.Asp165Asp	synonymous	Exon 2 of 13	ENSP00000316983.7	B3KT41

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1825 AN: 152014 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00332 AC: 827 AN: 249456 AF XY: 0.00239

Gnomad AFR exome AF: 0.0418

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00378

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000239

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00142 AC: 2081 AN: 1461844 Hom.: 32 Cov.: 34 AF XY: 0.00121 AC XY: 878 AN XY: 727212

African (AFR) AF: 0.0433 AC: 1451 AN: 33474

American (AMR) AF: 0.00230 AC: 103 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00247 AC: 98 AN: 39694

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.000156 AC: 174 AN: 1111984

Other (OTH) AF: 0.00376 AC: 227 AN: 60394

GnomAD4 genome AF: 0.0120 AC: 1829 AN: 152132 Hom.: 32 Cov.: 32 AF XY: 0.0116 AC XY: 863 AN XY: 74364

African (AFR) AF: 0.0413 AC: 1712 AN: 41498

American (AMR) AF: 0.00452 AC: 69 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00407 AC: 21 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68004

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00581 Hom.: 4

Bravo AF: 0.0143

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.78
DANN	Benign	0.54
PhyloP100		-0.49
Mutation Taster		=96/4	polymorphism

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: rs73130289; hg19: chr5-75428070;