rs198550

chr17-50575514-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.81

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]

ACMG classification

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/exons	MANE	UniProt
CACNA1G	NM_018896.5	c.1141-29A>G		intron_variant		ENST00000359106.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1G	ENST00000359106.10	c.1141-29A>G		intron_variant		1	NM_018896.5	A2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89291 AN: 151950 Hom.: 26924 Cov.: 32

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

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.: 35 AF XY: 0.557 AC XY: 391411 AN XY: 702558

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.: 32 AF XY: 0.593 AC XY: 44100 AN XY: 74344

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spinocerebellar ataxia type 42 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 14, 2021

- -

Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Other links and lift over

dbSNP: rs198550; hg19: chr17-48652875;