rs158199

Variant names:

• chr19-53999537-G-A
• rs158199
• NM_145814.2:c.407-97G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CACNG6	NM_145814.2	c.407-97G>A		intron_variant	Intron 2 of 3	ENST00000252729.7	NP_665813.1
CACNG6	NM_145815.2	c.406+1224G>A		intron_variant	Intron 2 of 2		NP_665814.1
CACNG6	NM_031897.3	c.331+6329G>A		intron_variant	Intron 1 of 1		NP_114103.2
CACNG6	NR_102308.2	n.124+1224G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.407-97G>A		intron_variant	Intron 2 of 3	1	NM_145814.2	ENSP00000252729.2
CACNG6	ENST00000346968.2	c.406+1224G>A		intron_variant	Intron 2 of 2	5		ENSP00000319097.2
CACNG6	ENST00000352529.1	c.331+6329G>A		intron_variant	Intron 1 of 1	5		ENSP00000319135.1

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

African (AFR) AF: 0.368 AC: 10579 AN: 28758

American (AMR) AF: 0.255 AC: 8275 AN: 32460

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2287 AN: 20624

East Asian (EAS) AF: 0.221 AC: 8437 AN: 38258

South Asian (SAS) AF: 0.163 AC: 11565 AN: 70926

European-Finnish (FIN) AF: 0.133 AC: 5088 AN: 38244

Middle Eastern (MID) AF: 0.197 AC: 1018 AN: 5164

European-Non Finnish (NFE) AF: 0.123 AC: 119963 AN: 978878

Other (OTH) AF: 0.150 AC: 8002 AN: 53304

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

African (AFR) AF: 0.359 AC: 14876 AN: 41404

American (AMR) AF: 0.244 AC: 3719 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1014 AN: 5150

South Asian (SAS) AF: 0.154 AC: 742 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1386 AN: 10588

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8554 AN: 67992

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.150 Hom.: 2685

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
PhyloP100		1.4
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: rs158199; hg19: chr19-54502791; COSMIC: COSV53168311;