19-54012620-C-T

Variant names:

• chr19-54012620-C-T
• rs459247
• NM_145814.2:c.*431C>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.*431C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 158,418 control chromosomes in the GnomAD database, including 7,928 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 0.28 (7522 hom., cov: 29)
  • Exomes 𝑓: 0.35 (406 hom.)
• Consequence: CACNG6 NM_145814.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 11 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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.*431C>T		3_prime_UTR	Exon 4 of 4	NP_665813.1
	CACNG6	NM_145815.2		c.*431C>T		3_prime_UTR	Exon 3 of 3	NP_665814.1
	CACNG6	NM_031897.3		c.*431C>T		3_prime_UTR	Exon 2 of 2	NP_114103.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG6	ENST00000252729.7	TSL:1 MANE Select	c.*431C>T		3_prime_UTR	Exon 4 of 4	ENSP00000252729.2
	CACNG6	ENST00000955412.1		c.*431C>T		3_prime_UTR	Exon 3 of 3	ENSP00000625471.1
	CACNG6	ENST00000352529.1	TSL:5	c.*431C>T		3_prime_UTR	Exon 2 of 2	ENSP00000319135.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42928 AN: 151480 Hom.: 7522 Cov.: 29

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.346 AC: 2358 AN: 6818 Hom.: 406 Cov.: 0 AF XY: 0.351 AC XY: 1213 AN XY: 3454

African (AFR) AF: 0.0824 AC: 28 AN: 340

American (AMR) AF: 0.227 AC: 44 AN: 194

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 95 AN: 268

East Asian (EAS) AF: 0.512 AC: 126 AN: 246

South Asian (SAS) AF: 0.345 AC: 20 AN: 58

European-Finnish (FIN) AF: 0.383 AC: 114 AN: 298

Middle Eastern (MID) AF: 0.375 AC: 9 AN: 24

European-Non Finnish (NFE) AF: 0.357 AC: 1761 AN: 4932

Other (OTH) AF: 0.352 AC: 161 AN: 458

GnomAD4 genome AF: 0.283 AC: 42930 AN: 151600 Hom.: 7522 Cov.: 29 AF XY: 0.288 AC XY: 21359 AN XY: 74038

African (AFR) AF: 0.0781 AC: 3232 AN: 41366

American (AMR) AF: 0.262 AC: 3980 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1219 AN: 3466

East Asian (EAS) AF: 0.540 AC: 2758 AN: 5112

South Asian (SAS) AF: 0.423 AC: 2034 AN: 4810

European-Finnish (FIN) AF: 0.384 AC: 4023 AN: 10486

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24646 AN: 67860

Other (OTH) AF: 0.318 AC: 669 AN: 2102

Alfa AF: 0.336 Hom.: 30073

Bravo AF: 0.264

Asia WGS AF: 0.455 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		0.19
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: rs459247; hg19: chr19-54515874;