rs4806481

Variant names:

• chr19-53994033-C-T
• rs4806481
• NM_145814.2:c.331+825C>T

Variant summary

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

The NM_145814.2(CACNG6):​c.331+825C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,820 control chromosomes in the GnomAD database, including 7,266 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 0.29 (7266 hom., cov: 31)
• Consequence: CACNG6 NM_145814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	NM_145814.2	MANE Select	c.331+825C>T		intron	N/A	NP_665813.1	Q9BXT2
	CACNG6	NM_145815.2		c.331+825C>T		intron	N/A	NP_665814.1	A6NFR2
	CACNG6	NM_031897.3		c.331+825C>T		intron	N/A	NP_114103.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	ENST00000252729.7	TSL:1 MANE Select	c.331+825C>T		intron	N/A	ENSP00000252729.2	Q9BXT2
	CACNG6	ENST00000955412.1		c.331+825C>T		intron	N/A	ENSP00000625471.1
	CACNG6	ENST00000346968.2	TSL:5	c.331+825C>T		intron	N/A	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44410 AN: 151702 Hom.: 7261 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.293 AC: 44420 AN: 151820 Hom.: 7266 Cov.: 31 AF XY: 0.292 AC XY: 21658 AN XY: 74190

African (AFR) AF: 0.156 AC: 6453 AN: 41390

American (AMR) AF: 0.326 AC: 4971 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1503 AN: 3466

East Asian (EAS) AF: 0.441 AC: 2264 AN: 5128

South Asian (SAS) AF: 0.348 AC: 1671 AN: 4806

European-Finnish (FIN) AF: 0.253 AC: 2666 AN: 10546

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23599 AN: 67914

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.330 Hom.: 7454

Bravo AF: 0.294

Asia WGS AF: 0.400 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		-0.18
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: rs4806481; hg19: chr19-54497287;