Genetic Variant CACNG6:c.*431C>T (chr19-54012620-C-T) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Publications

11 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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CACNG6	NM_145814.2 link	c.*431C>T	3_prime_UTR_variant	Exon 4 of 4	ENST00000252729.7	NP_665813.1	Q9BXT2
CACNG6	NR_102308.2 link	n.794C>T	non_coding_transcript_exon_variant	Exon 3 of 3
CACNG6	NM_145815.2 link	c.*431C>T	3_prime_UTR_variant	Exon 3 of 3		NP_665814.1	Q9BXT2A6NFR2
CACNG6	NM_031897.3 link	c.*431C>T	3_prime_UTR_variant	Exon 2 of 2		NP_114103.2	Q9BXT2A6NP74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7 link	c.*431C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_145814.2	ENSP00000252729.2		Q9BXT2
CACNG6	ENST00000352529.1 link	c.*431C>T		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000319135.1		A6NP74

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42928

AN:

151480

Hom.:

7522

Cov.:

show subpopulations

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.:

AF XY:

0.351

AC XY:

1213

AN XY:

3454

show subpopulations

African (AFR)

AF:

0.0824

AC:

AN:

340

American (AMR)

AF:

0.227

AC:

AN:

194

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

AN:

268

East Asian (EAS)

AF:

0.512

AC:

126

AN:

246

South Asian (SAS)

AF:

0.345

AC:

AN:

European-Finnish (FIN)

AF:

0.383

AC:

114

AN:

298

Middle Eastern (MID)

AF:

0.375

AC:

AN:

European-Non Finnish (NFE)

AF:

0.357

AC:

1761

AN:

4932

Other (OTH)

AF:

0.352

AC:

161

AN:

458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.283

AC:

42930

AN:

151600

Hom.:

7522

Cov.:

AF XY:

0.288

AC XY:

21359

AN XY:

74038

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1407

2814

4220

5627

7034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.336

Hom.:

30073

Bravo

AF:

0.264

Asia WGS

AF:

0.455

AC:

1584

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.19

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over