dbSNP rs198550: CACNA1G:c.1141-29A>G (chr17-50575514-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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

GnomAD3 exomes

AF:

0.600

AC:

133853

AN:

222978

Hom.:

41433

AF XY:

0.598

AC XY:

72110

AN XY:

120682

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 SAS exome

AF:

0.671

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

Gnomad4 AFR exome

AF:

0.640

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.948

Gnomad4 SAS exome

AF:

0.673

Gnomad4 FIN exome

AF:

0.564

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.588

AC:

89388

AN:

152068

Hom.:

26971

Cov.:

AF XY:

0.593

AC XY:

44100

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.639

Gnomad4 AMR

AF:

0.579

Gnomad4 ASJ

AF:

0.496

Gnomad4 EAS

AF:

0.935

Gnomad4 SAS

AF:

0.694

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.574

Alfa

AF:

0.542

Hom.:

40810

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

Mar 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

DANN

Benign

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over