19-54007463-A-G

Variant names:

• chr19-54007463-A-G
• rs192808
• NM_145814.2:c.545-4488A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145814.2(CACNG6):​c.545-4488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,204 control chromosomes in the GnomAD database, including 43,098 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 0.75 (43098 hom., cov: 33)
• Consequence: CACNG6 NM_145814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145814.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	NM_145814.2	MANE Select	c.545-4488A>G		intron	N/A	NP_665813.1
	CACNG6	NM_145815.2		c.407-4488A>G		intron	N/A	NP_665814.1
	CACNG6	NM_031897.3		c.332-4488A>G		intron	N/A	NP_114103.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	ENST00000252729.7	TSL:1 MANE Select	c.545-4488A>G		intron	N/A	ENSP00000252729.2
	CACNG6	ENST00000346968.2	TSL:5	c.407-4488A>G		intron	N/A	ENSP00000319097.2
	CACNG6	ENST00000352529.1	TSL:5	c.332-4488A>G		intron	N/A	ENSP00000319135.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113595 AN: 152086 Hom.: 43048 Cov.: 33

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.747 AC: 113699 AN: 152204 Hom.: 43098 Cov.: 33 AF XY: 0.744 AC XY: 55356 AN XY: 74402

African (AFR) AF: 0.849 AC: 35283 AN: 41548

American (AMR) AF: 0.763 AC: 11677 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4954 AN: 5188

South Asian (SAS) AF: 0.679 AC: 3279 AN: 4830

European-Finnish (FIN) AF: 0.626 AC: 6610 AN: 10564

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.691 AC: 47018 AN: 67996

Other (OTH) AF: 0.737 AC: 1556 AN: 2112

Alfa AF: 0.711 Hom.: 61006

Bravo AF: 0.766

Asia WGS AF: 0.830 AC: 2883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		-0.032
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: rs192808; hg19: chr19-54510717;