rs2291068

Variant names:

• chr19-54012307-A-G
• rs2291068
• NM_145814.2:c.*118A>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.*118A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 492,142 control chromosomes in the GnomAD database, including 2,117 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 0.092 (1178 hom., cov: 30)
  • Exomes 𝑓: 0.054 (939 hom.)
• Consequence: CACNG6 NM_145814.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG6	NM_145814.2	c.*118A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000252729.7	NP_665813.1
CACNG6	NR_102308.2	n.481A>G		non_coding_transcript_exon_variant	Exon 3 of 3
CACNG6	NM_145815.2	c.*118A>G		3_prime_UTR_variant	Exon 3 of 3		NP_665814.1
CACNG6	NM_031897.3	c.*118A>G		3_prime_UTR_variant	Exon 2 of 2		NP_114103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.*118A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_145814.2	ENSP00000252729.2
CACNG6	ENST00000352529.1	c.*118A>G		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000319135.1
CACNG6	ENST00000346968.2	c.*118A>G		downstream_gene_variant		5		ENSP00000319097.2

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 13928 AN: 151040 Hom.: 1180 Cov.: 30

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0734

GnomAD4 exome AF: 0.0539 AC: 18367 AN: 340984 Hom.: 939 Cov.: 4 AF XY: 0.0496 AC XY: 8907 AN XY: 179424

African (AFR) AF: 0.212 AC: 2030 AN: 9564

American (AMR) AF: 0.107 AC: 1794 AN: 16726

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 121 AN: 10546

East Asian (EAS) AF: 0.184 AC: 4958 AN: 26992

South Asian (SAS) AF: 0.0205 AC: 291 AN: 14228

European-Finnish (FIN) AF: 0.0648 AC: 1718 AN: 26524

Middle Eastern (MID) AF: 0.0358 AC: 109 AN: 3048

European-Non Finnish (NFE) AF: 0.0296 AC: 6324 AN: 213302

Other (OTH) AF: 0.0510 AC: 1022 AN: 20054

GnomAD4 genome AF: 0.0922 AC: 13935 AN: 151158 Hom.: 1178 Cov.: 30 AF XY: 0.0905 AC XY: 6677 AN XY: 73818

African (AFR) AF: 0.218 AC: 8968 AN: 41138

American (AMR) AF: 0.0758 AC: 1146 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3464

East Asian (EAS) AF: 0.151 AC: 772 AN: 5114

South Asian (SAS) AF: 0.0212 AC: 101 AN: 4764

European-Finnish (FIN) AF: 0.0623 AC: 651 AN: 10442

Middle Eastern (MID) AF: 0.0138 AC: 4 AN: 290

European-Non Finnish (NFE) AF: 0.0301 AC: 2042 AN: 67830

Other (OTH) AF: 0.0727 AC: 152 AN: 2092

Alfa AF: 0.0509 Hom.: 328

Bravo AF: 0.103

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.33
DANN	Benign	0.46
PhyloP100		-1.3
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: rs2291068; hg19: chr19-54515561;