rs450227

Variant names:

• chr19-54009728-G-A
• rs450227
• NM_145814.2:c.545-2223G>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.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
• Publications: 1 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=-0.86).
• 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 rank	MANE	Protein	UniProt
CACNG6	NM_145814.2	c.545-2223G>A		intron_variant	Intron 3 of 3	ENST00000252729.7	NP_665813.1
CACNG6	NM_145815.2	c.407-2223G>A		intron_variant	Intron 2 of 2		NP_665814.1
CACNG6	NM_031897.3	c.332-2223G>A		intron_variant	Intron 1 of 1		NP_114103.2
CACNG6	NR_102308.2	n.125-2223G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.545-2223G>A		intron_variant	Intron 3 of 3	1	NM_145814.2	ENSP00000252729.2
CACNG6	ENST00000346968.2	c.407-2223G>A		intron_variant	Intron 2 of 2	5		ENSP00000319097.2
CACNG6	ENST00000352529.1	c.332-2223G>A		intron_variant	Intron 1 of 1	5		ENSP00000319135.1

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

African (AFR) AF: 0.277 AC: 11408 AN: 41182

American (AMR) AF: 0.0615 AC: 931 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 33 AN: 3466

East Asian (EAS) AF: 0.133 AC: 670 AN: 5022

South Asian (SAS) AF: 0.0181 AC: 87 AN: 4794

European-Finnish (FIN) AF: 0.0611 AC: 637 AN: 10432

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0316 AC: 2145 AN: 67906

Other (OTH) AF: 0.0849 AC: 178 AN: 2096

Alfa AF: 0.0860 Hom.: 390

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
PhyloP100		-0.20
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: rs450227; hg19: chr19-54512982;