rs714822

Positions:

• chr16-24355195-C-G
• chr16-24355195-C-T

Variant summary

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

The NM_006539.4(CACNG3):​c.436+222C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,782 control chromosomes in the GnomAD database, including 1,679 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 0.15 (1679 hom., cov: 32)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.436+222C>G		intron_variant		ENST00000005284.4	NP_006530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG3	ENST00000005284.4	c.436+222C>G		intron_variant		1	NM_006539.4	ENSP00000005284	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22067 AN: 151664 Hom.: 1678 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0841

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.145 AC: 22073 AN: 151782 Hom.: 1679 Cov.: 32 AF XY: 0.148 AC XY: 11004 AN XY: 74142

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0845

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0708 Hom.: 93

Bravo AF: 0.140

Asia WGS AF: 0.116 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.54

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: rs714822; hg19: chr16-24366516;