16-24260736-T-C

Variant names:

• chr16-24260736-T-C
• rs11860647
• NM_006539.4:c.211+3771T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006539.4(CACNG3):​c.211+3771T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,122 control chromosomes in the GnomAD database, including 40,836 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 0.72 (40836 hom., cov: 32)
• Consequence: CACNG3 NM_006539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG3	NM_006539.4	c.211+3771T>C		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+3771T>C		intron_variant	Intron 1 of 3	1	NM_006539.4	ENSP00000005284.4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110113 AN: 152004 Hom.: 40791 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.724 AC: 110211 AN: 152122 Hom.: 40836 Cov.: 32 AF XY: 0.722 AC XY: 53656 AN XY: 74348

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.718

Alfa AF: 0.687 Hom.: 8347

Bravo AF: 0.735

Asia WGS AF: 0.726 AC: 2528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.4
DANN	Benign	0.74

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: rs11860647; hg19: chr16-24272057;