rs2238521

Variant names:

• chr16-24337270-G-A
• rs2238521
• NM_006539.4:c.212-9464G>A

Variant summary

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

The NM_006539.4(CACNG3):​c.212-9464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,008 control chromosomes in the GnomAD database, including 6,046 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 0.28 (6046 hom., cov: 31)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.74
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.212-9464G>A		intron_variant	Intron 1 of 3	ENST00000005284.4	NP_006530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG3	ENST00000005284.4	c.212-9464G>A		intron_variant	Intron 1 of 3	1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42054 AN: 151890 Hom.: 6041 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.277 AC: 42103 AN: 152008 Hom.: 6046 Cov.: 31 AF XY: 0.278 AC XY: 20642 AN XY: 74314

African (AFR) AF: 0.292 AC: 12117 AN: 41466

American (AMR) AF: 0.377 AC: 5748 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1208 AN: 3464

East Asian (EAS) AF: 0.303 AC: 1564 AN: 5164

South Asian (SAS) AF: 0.267 AC: 1284 AN: 4814

European-Finnish (FIN) AF: 0.271 AC: 2868 AN: 10570

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.241 AC: 16393 AN: 67978

Other (OTH) AF: 0.276 AC: 581 AN: 2102

Alfa AF: 0.260 Hom.: 2938

Bravo AF: 0.287

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.018
DANN	Benign	0.77
PhyloP100		-5.7
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: rs2238521; hg19: chr16-24348591;