16-24269953-G-C

Variant names:

• chr16-24269953-G-C
• rs2283550
• NM_006539.4:c.211+12988G>C

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+12988G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,254 control chromosomes in the GnomAD database, including 3,053 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 0.20 (3053 hom., cov: 31)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006539.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG3	NM_006539.4	MANE Select	c.211+12988G>C		intron	N/A	NP_006530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG3	ENST00000005284.4	TSL:1 MANE Select	c.211+12988G>C		intron	N/A	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30206 AN: 151140 Hom.: 3048 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.200 AC: 30238 AN: 151254 Hom.: 3053 Cov.: 31 AF XY: 0.198 AC XY: 14620 AN XY: 73836

African (AFR) AF: 0.219 AC: 9013 AN: 41234

American (AMR) AF: 0.148 AC: 2250 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3472

East Asian (EAS) AF: 0.133 AC: 686 AN: 5168

South Asian (SAS) AF: 0.168 AC: 806 AN: 4790

European-Finnish (FIN) AF: 0.174 AC: 1781 AN: 10244

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14501 AN: 67808

Other (OTH) AF: 0.188 AC: 395 AN: 2102

Alfa AF: 0.201 Hom.: 410

Bravo AF: 0.199

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.89
DANN	Benign	0.30
PhyloP100		-0.40
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: rs2283550; hg19: chr16-24281274;