rs158199

chr19-53999537-G-A

Variant summary

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

The NM_145814.2(CACNG6):c.407-97G>A 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 1,418,624 control chromosomes in the GnomAD database, including 17,581 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 0.21 (3938 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13643 hom.)
• Consequence: CACNG6 NM_145814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

Genes affected

CACNG6 (HGNC:13625): (calcium voltage-gated channel auxiliary subunit gamma 6) Voltage-dependent calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members that function as transmembrane AMPA receptor regulatory proteins (TARPs). Alternative splicing results in multiple transcript variants. Variants in this gene have been associated with aspirin-intolerant asthma. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG6	NM_145814.2	c.407-97G>A		intron_variant		ENST00000252729.7
CACNG6	NM_031897.3	c.331+6329G>A		intron_variant
CACNG6	NM_145815.2	c.406+1224G>A		intron_variant
CACNG6	NR_102308.2	n.124+1224G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG6	ENST00000252729.7	c.407-97G>A		intron_variant		1	NM_145814.2	P1
CACNG6	ENST00000346968.2	c.406+1224G>A		intron_variant		5
CACNG6	ENST00000352529.1	c.331+6329G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31115 AN: 151890 Hom.: 3921 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.138 AC: 175214 AN: 1266616 Hom.: 13643 AF XY: 0.138 AC XY: 86963 AN XY: 629370

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.205 AC: 31184 AN: 152008 Hom.: 3938 Cov.: 32 AF XY: 0.205 AC XY: 15248 AN XY: 74326

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.187

Alfa AF: 0.149 Hom.: 1669

Bravo AF: 0.221

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.7
Dann	Benign	0.77

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: rs158199; hg19: chr19-54502791; COSMIC: COSV53168311;