rs2291068

Positions:

• chr19-54012307-A-G

Variant summary

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

The NM_145814.2(CACNG6):​c.*118A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 492,142 control chromosomes in the GnomAD database, including 2,117 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 0.092 (1178 hom., cov: 30)
  • Exomes 𝑓: 0.054 (939 hom.)
• Consequence: CACNG6 NM_145814.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG6	NM_145814.2	c.*118A>G		3_prime_UTR_variant	4/4	ENST00000252729.7	NP_665813.1
CACNG6	NM_031897.3	c.*118A>G		3_prime_UTR_variant	2/2		NP_114103.2
CACNG6	NM_145815.2	c.*118A>G		3_prime_UTR_variant	3/3		NP_665814.1
CACNG6	NR_102308.2	n.481A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.*118A>G		3_prime_UTR_variant	4/4	1	NM_145814.2	ENSP00000252729	P1
CACNG6	ENST00000352529.1	c.*118A>G		3_prime_UTR_variant	2/2	5		ENSP00000319135

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 13928 AN: 151040 Hom.: 1180 Cov.: 30

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0734

GnomAD4 exome AF: 0.0539 AC: 18367 AN: 340984 Hom.: 939 Cov.: 4 AF XY: 0.0496 AC XY: 8907 AN XY: 179424

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0205

Gnomad4 FIN exome AF: 0.0648

Gnomad4 NFE exome AF: 0.0296

Gnomad4 OTH exome AF: 0.0510

GnomAD4 genome AF: 0.0922 AC: 13935 AN: 151158 Hom.: 1178 Cov.: 30 AF XY: 0.0905 AC XY: 6677 AN XY: 73818

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0727

Alfa AF: 0.0552 Hom.: 244

Bravo AF: 0.103

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.33
DANN	Benign	0.46

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: rs2291068; hg19: chr19-54515561;