rs450227

Positions:

• chr19-54009728-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.545-2223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,248 control chromosomes in the GnomAD database, including 1,809 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 0.11 (1809 hom., cov: 29)
• Consequence: CACNG6 NM_145814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG6	NM_145814.2	c.545-2223G>A		intron_variant		ENST00000252729.7	NP_665813.1
CACNG6	NM_031897.3	c.332-2223G>A		intron_variant			NP_114103.2
CACNG6	NM_145815.2	c.407-2223G>A		intron_variant			NP_665814.1
CACNG6	NR_102308.2	n.125-2223G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.545-2223G>A		intron_variant		1	NM_145814.2	ENSP00000252729	P1
CACNG6	ENST00000346968.2	c.407-2223G>A		intron_variant		5		ENSP00000319097
CACNG6	ENST00000352529.1	c.332-2223G>A		intron_variant		5		ENSP00000319135

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16073 AN: 151128 Hom.: 1802 Cov.: 29

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0183

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.0868

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

GnomAD4 genome AF: 0.107 AC: 16108 AN: 151248 Hom.: 1809 Cov.: 29 AF XY: 0.104 AC XY: 7693 AN XY: 73810

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.00952

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0181

Gnomad4 FIN AF: 0.0611

Gnomad4 NFE AF: 0.0316

Gnomad4 OTH AF: 0.0849

Alfa AF: 0.100 Hom.: 243

Bravo AF: 0.116

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.67

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: rs450227; hg19: chr19-54512982;