19-53993721-C-G

Position:

• chr19-53993721-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145814.2(CACNG6):​c.331+513C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 149,962 control chromosomes in the GnomAD database, including 3,367 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 0.20 (3367 hom., cov: 25)
• Consequence: CACNG6 NM_145814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.752

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=-0.84).
• 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	UniProt
CACNG6	NM_145814.2	c.331+513C>G		intron_variant		ENST00000252729.7
CACNG6	NM_031897.3	c.331+513C>G		intron_variant
CACNG6	NM_145815.2	c.331+513C>G		intron_variant
CACNG6	NR_102308.2	n.49+2524C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG6	ENST00000252729.7	c.331+513C>G		intron_variant		1	NM_145814.2	P1
CACNG6	ENST00000346968.2	c.331+513C>G		intron_variant		5
CACNG6	ENST00000352529.1	c.331+513C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30090 AN: 149846 Hom.: 3367 Cov.: 25

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.201 AC: 30094 AN: 149962 Hom.: 3367 Cov.: 25 AF XY: 0.198 AC XY: 14484 AN XY: 73110

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.195

Alfa AF: 0.0907 Hom.: 128

Bravo AF: 0.210

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.57

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: rs158194; hg19: chr19-54496975;