rs12932291

chr16-24362448-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 16-24362448-C-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,592 control chromosomes in the GnomAD database, including 2,830 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 0.19 (2818 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12 hom.)
• Consequence: CACNG3 NM_006539.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768

Genes affected

CACNG3 (HGNC:1407): (calcium voltage-gated channel auxiliary subunit gamma 3) The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family. This gene is a susceptibility locus for childhood absence epilepsy. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG3	NM_006539.4			downstream_gene_variant		ENST00000005284.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG3	ENST00000005284.4			downstream_gene_variant		1	NM_006539.4	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29023 AN: 151948 Hom.: 2816 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0542

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.219 AC: 115 AN: 526 Hom.: 12 Cov.: 0 AF XY: 0.226 AC XY: 70 AN XY: 310

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.191 AC: 29042 AN: 152066 Hom.: 2818 Cov.: 32 AF XY: 0.193 AC XY: 14334 AN XY: 74328

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0545

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.188

Alfa AF: 0.192 Hom.: 374

Bravo AF: 0.186

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	13
Dann	Benign	0.65

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: rs12932291; hg19: chr16-24373769; COSMIC: COSV50088461;