NM_006539.4:c.295+1295G>A

Variant names:

• chr16-24348112-G-A
• rs8048828
• NM_006539.4:c.295+1295G>A

Variant summary

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

The NM_006539.4(CACNG3):​c.295+1295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,998 control chromosomes in the GnomAD database, including 28,612 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 0.61 (28612 hom., cov: 32)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.295+1295G>A		intron_variant	Intron 2 of 3	ENST00000005284.4	NP_006530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG3	ENST00000005284.4	c.295+1295G>A		intron_variant	Intron 2 of 3	1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92659 AN: 151880 Hom.: 28594 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.610 AC: 92727 AN: 151998 Hom.: 28612 Cov.: 32 AF XY: 0.608 AC XY: 45171 AN XY: 74300

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.613

Alfa AF: 0.575 Hom.: 13184

Bravo AF: 0.625

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.29

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: rs8048828; hg19: chr16-24359433;