rs2238499

Variant names:

• chr16-24271278-G-A
• rs2238499
• NM_006539.4:c.211+14313G>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.211+14313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,004 control chromosomes in the GnomAD database, including 5,026 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 0.25 (5026 hom., cov: 32)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.211+14313G>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.211+14313G>A		intron_variant	Intron 1 of 3	1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38258 AN: 151884 Hom.: 5027 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.252 AC: 38261 AN: 152004 Hom.: 5026 Cov.: 32 AF XY: 0.256 AC XY: 18986 AN XY: 74296

African (AFR) AF: 0.173 AC: 7166 AN: 41444

American (AMR) AF: 0.262 AC: 4000 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1098 AN: 3472

East Asian (EAS) AF: 0.183 AC: 945 AN: 5172

South Asian (SAS) AF: 0.360 AC: 1731 AN: 4806

European-Finnish (FIN) AF: 0.329 AC: 3482 AN: 10574

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19000 AN: 67960

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.267 Hom.: 10838

Bravo AF: 0.241

Asia WGS AF: 0.276 AC: 964 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	6.4
DANN	Benign	0.67
PhyloP100		0.48
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: rs2238499; hg19: chr16-24282599;