17-50569650-T-G

Variant names:

• chr17-50569650-T-G
• rs12946808
• NM_018896.5:c.489-56T>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.489-56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,259,974 control chromosomes in the GnomAD database, including 169,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16734 hom., cov: 30)
  • Exomes 𝑓: 0.51 (152781 hom.)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.249

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=-0.61).
• BP6: Variant 17-50569650-T-G is Benign according to our data. Variant chr17-50569650-T-G is described in ClinVar as [Benign]. Clinvar id is 1192601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.489-56T>G		intron_variant	Intron 3 of 37	ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.489-56T>G		intron_variant	Intron 3 of 37	1	NM_018896.5	ENSP00000352011.5
CACNA1G	ENST00000507510.6	c.489-56T>G		intron_variant	Intron 3 of 36	1		ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67297 AN: 151696 Hom.: 16736 Cov.: 30

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.514 AC: 569253 AN: 1108160 Hom.: 152781 AF XY: 0.521 AC XY: 289380 AN XY: 555712

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.428

Gnomad4 EAS exome AF: 0.931

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.443 AC: 67295 AN: 151814 Hom.: 16734 Cov.: 30 AF XY: 0.452 AC XY: 33506 AN XY: 74180

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.457

Alfa AF: 0.457 Hom.: 2226

Bravo AF: 0.434

Asia WGS AF: 0.716 AC: 2487 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	-0.61
CADD	Benign	16
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12946808; hg19: chr17-48647011;