Genetic Variant CACNG6:c.332-881A>G (chr19-53997358-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145814.2(CACNG6):c.332-881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,708 control chromosomes in the GnomAD database, including 10,231 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 0.32 ( 10231 hom., cov: 30)

Consequence

CACNG6
NM_145814.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

7 publications found

Variant links:

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]

CACNG6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNG6	NM_145814.2	MANE Select	c.332-881A>G	intron	N/A	NP_665813.1	Q9BXT2
CACNG6	NM_145815.2		c.332-881A>G	intron	N/A	NP_665814.1	A6NFR2
CACNG6	NM_031897.3		c.331+4150A>G	intron	N/A	NP_114103.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNG6	ENST00000252729.7	TSL:1 MANE Select	c.332-881A>G	intron	N/A	ENSP00000252729.2	Q9BXT2
CACNG6	ENST00000955412.1		c.332-2276A>G	intron	N/A	ENSP00000625471.1
CACNG6	ENST00000346968.2	TSL:5	c.332-881A>G	intron	N/A	ENSP00000319097.2	A6NFR2

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48742

AN:

151594

Hom.:

10195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.202

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.296

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

GnomAD4 genome

AF:

0.322

AC:

48839

AN:

151708

Hom.:

10231

Cov.:

AF XY:

0.319

AC XY:

23630

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.599

AC:

24785

AN:

41352

American (AMR)

AF:

0.319

AC:

4862

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

567

AN:

3466

East Asian (EAS)

AF:

0.294

AC:

1516

AN:

5162

South Asian (SAS)

AF:

0.200

AC:

963

AN:

4808

European-Finnish (FIN)

AF:

0.199

AC:

2081

AN:

10442

Middle Eastern (MID)

AF:

0.217

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.196

AC:

13308

AN:

67932

Other (OTH)

AF:

0.296

AC:

625

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1434

2868

4302

5736

7170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.226

Hom.:

9361

Bravo

AF:

0.343

Asia WGS

AF:

0.263

AC:

913

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.4

(source)

DANN

Benign

0.52

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over