rs3810244

Positions:

• chr19-53992678-A-G
• chr19-53992678-A-T

Variant summary

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

The NM_145814.2(CACNG6):​c.-200A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 374,080 control chromosomes in the GnomAD database, including 84,908 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 0.68 (35273 hom., cov: 30)
  • Exomes 𝑓: 0.67 (49635 hom.)
• Consequence: CACNG6 NM_145814.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG6	NM_145814.2	c.-200A>G		5_prime_UTR_variant	1/4	ENST00000252729.7
CACNG6	NM_031897.3	c.-200A>G		5_prime_UTR_variant	1/2
CACNG6	NM_145815.2	c.-200A>G		5_prime_UTR_variant	1/3
CACNG6	NR_102308.2	n.49+1481A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG6	ENST00000252729.7	c.-200A>G		5_prime_UTR_variant	1/4	1	NM_145814.2	P1
CACNG6	ENST00000352529.1	c.-200A>G		5_prime_UTR_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103234 AN: 151736 Hom.: 35241 Cov.: 30

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.667 AC: 148158 AN: 222226 Hom.: 49635 Cov.: 3 AF XY: 0.668 AC XY: 75457 AN XY: 112994

Gnomad4 AFR exome AF: 0.747

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.694

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.680 AC: 103319 AN: 151854 Hom.: 35273 Cov.: 30 AF XY: 0.675 AC XY: 50085 AN XY: 74212

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.686

Alfa AF: 0.672 Hom.: 42359

Bravo AF: 0.691

Asia WGS AF: 0.715 AC: 2486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.25

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: rs3810244; hg19: chr19-54495932;