rs11648890

Variant names:

• chr16-24362582-G-A
• rs11648890
• NM_006539.4:c.*719G>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.*719G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,168 control chromosomes in the GnomAD database, including 4,868 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 (4847 hom., cov: 31)
  • Exomes 𝑓: 0.31 (21 hom.)
• Consequence: CACNG3 NM_006539.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.*719G>A		downstream_gene_variant		ENST00000005284.4	NP_006530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG3	ENST00000005284.4	c.*719G>A		downstream_gene_variant		1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37545 AN: 151614 Hom.: 4844 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.310 AC: 135 AN: 436 Hom.: 21 Cov.: 0 AF XY: 0.303 AC XY: 80 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.307 AC: 130 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.248 AC: 37562 AN: 151732 Hom.: 4847 Cov.: 31 AF XY: 0.252 AC XY: 18657 AN XY: 74130

African (AFR) AF: 0.186 AC: 7692 AN: 41376

American (AMR) AF: 0.290 AC: 4417 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1813 AN: 5100

South Asian (SAS) AF: 0.263 AC: 1262 AN: 4804

European-Finnish (FIN) AF: 0.309 AC: 3249 AN: 10508

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17181 AN: 67942

Other (OTH) AF: 0.259 AC: 545 AN: 2104

Alfa AF: 0.252 Hom.: 7499

Bravo AF: 0.245

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.29
PhyloP100		0.55
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: rs11648890; hg19: chr16-24373903; COSMIC: COSV50073462;