rs4806481

chr19-53994033-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG6	NM_145814.2	c.331+825C>T		intron_variant		ENST00000252729.7
CACNG6	NM_031897.3	c.331+825C>T		intron_variant
CACNG6	NM_145815.2	c.331+825C>T		intron_variant
CACNG6	NR_102308.2	n.49+2836C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG6	ENST00000252729.7	c.331+825C>T		intron_variant		1	NM_145814.2	P1
CACNG6	ENST00000346968.2	c.331+825C>T		intron_variant		5
CACNG6	ENST00000352529.1	c.331+825C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.328

Alfa AF: 0.330 Hom.: 5384

Bravo AF: 0.294

Asia WGS AF: 0.400 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.3
Dann	Benign	0.78

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: rs4806481; hg19: chr19-54497287;