16-24292253-C-T

Variant names:

• chr16-24292253-C-T
• rs11640935
• NM_006539.4:c.211+35288C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006539.4(CACNG3):​c.211+35288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,038 control chromosomes in the GnomAD database, including 3,461 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 (3461 hom., cov: 32)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.211+35288C>T		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+35288C>T		intron_variant	Intron 1 of 3	1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30301 AN: 151918 Hom.: 3459 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.199 AC: 30312 AN: 152038 Hom.: 3461 Cov.: 32 AF XY: 0.195 AC XY: 14513 AN XY: 74308

African (AFR) AF: 0.107 AC: 4422 AN: 41464

American (AMR) AF: 0.150 AC: 2299 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.123 AC: 633 AN: 5150

South Asian (SAS) AF: 0.175 AC: 840 AN: 4812

European-Finnish (FIN) AF: 0.209 AC: 2215 AN: 10574

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18572 AN: 67966

Other (OTH) AF: 0.195 AC: 410 AN: 2106

Alfa AF: 0.236 Hom.: 7405

Bravo AF: 0.190

Asia WGS AF: 0.145 AC: 502 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.42
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: rs11640935; hg19: chr16-24303574;