rs198550

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018896.5(CACNA1G):c.1141-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,575,772 control chromosomes in the GnomAD database, including 250,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26971 hom., cov: 32)

Exomes 𝑓: 0.55 ( 223895 hom. )

Consequence

CACNA1G
NM_018896.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.81

Publications

13 publications found

Variant links:

Genes affected

CACNA1G (HGNC:1394): (calcium voltage-gated channel subunit alpha1 G) Voltage-sensitive calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division, and cell death. This gene encodes a T-type, low-voltage activated calcium channel. The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Many alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2011]

CACNA1G Gene-Disease associations (from GenCC):

spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, Ambry Genetics
spinocerebellar ataxia type 42
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Illumina
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

CACNA1G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-50575514-A-G is Benign according to our data. Variant chr17-50575514-A-G is described in ClinVar as Benign. ClinVar VariationId is 1192603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5 link	c.1141-29A>G		intron_variant	Intron 7 of 37	ENST00000359106.10	NP_061496.2	O43497-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10 link	c.1141-29A>G		intron_variant	Intron 7 of 37	1	NM_018896.5	ENSP00000352011.5		O43497-1
CACNA1G	ENST00000507510.6 link	c.1141-29A>G		intron_variant	Intron 7 of 36	1		ENSP00000423112.2		O43497-12

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89291

AN:

151950

Hom.:

26924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.638

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.935

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.569

GnomAD2 exomes

AF:

0.600

AC:

133853

AN:

222978

AF XY:

0.598

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.490

Gnomad EAS exome

AF:

0.938

Gnomad FIN exome

AF:

0.569

Gnomad NFE exome

AF:

0.530

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.554

AC:

789265

AN:

1423704

Hom.:

223895

Cov.:

AF XY:

0.557

AC XY:

391411

AN XY:

702558

show subpopulations

African (AFR)

AF:

0.640

AC:

20849

AN:

32568

American (AMR)

AF:

0.618

AC:

25749

AN:

41642

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

12114

AN:

24706

East Asian (EAS)

AF:

0.948

AC:

36960

AN:

38984

South Asian (SAS)

AF:

0.673

AC:

55269

AN:

82066

European-Finnish (FIN)

AF:

0.564

AC:

29402

AN:

52112

Middle Eastern (MID)

AF:

0.511

AC:

2138

AN:

4186

European-Non Finnish (NFE)

AF:

0.527

AC:

573869

AN:

1088958

Other (OTH)

AF:

0.563

AC:

32915

AN:

58482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

19179

38358

57538

76717

95896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16850

33700

50550

67400

84250

<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:

0.588

AC:

89388

AN:

152068

Hom.:

26971

Cov.:

AF XY:

0.593

AC XY:

44100

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.639

AC:

26497

AN:

41466

American (AMR)

AF:

0.579

AC:

8845

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1720

AN:

3470

East Asian (EAS)

AF:

0.935

AC:

4839

AN:

5178

South Asian (SAS)

AF:

0.694

AC:

3354

AN:

4830

European-Finnish (FIN)

AF:

0.572

AC:

6044

AN:

10570

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.536

AC:

36444

AN:

67958

Other (OTH)

AF:

0.574

AC:

1210

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1866

3733

5599

7466

9332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.553

Hom.:

98534

Bravo

AF:

0.589

Asia WGS

AF:

0.809

AC:

2809

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinocerebellar ataxia type 42

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.053

(source)

DANN

Benign

0.35

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over