chr17-50568250-G-T

Variant names:

• chr17-50568250-G-T
• rs198545
• NM_018896.5:c.243-620G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018896.5(CACNA1G):​c.243-620G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,012 control chromosomes in the GnomAD database, including 487 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 0.072 (487 hom., cov: 32)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018896.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1G	NM_018896.5	MANE Select	c.243-620G>T		intron	N/A	NP_061496.2
	CACNA1G	NM_198377.3		c.243-620G>T		intron	N/A	NP_938191.2
	CACNA1G	NM_198396.3		c.243-620G>T		intron	N/A	NP_938406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1G	ENST00000359106.10	TSL:1 MANE Select	c.243-620G>T		intron	N/A	ENSP00000352011.5
	CACNA1G	ENST00000507336.5	TSL:1	c.243-620G>T		intron	N/A	ENSP00000420918.1
	CACNA1G	ENST00000507510.6	TSL:1	c.243-620G>T		intron	N/A	ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10936 AN: 151894 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0699

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0722 AC: 10970 AN: 152012 Hom.: 487 Cov.: 32 AF XY: 0.0713 AC XY: 5301 AN XY: 74318

African (AFR) AF: 0.0942 AC: 3902 AN: 41436

American (AMR) AF: 0.0726 AC: 1109 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3466

East Asian (EAS) AF: 0.0301 AC: 155 AN: 5148

South Asian (SAS) AF: 0.0439 AC: 211 AN: 4810

European-Finnish (FIN) AF: 0.0749 AC: 794 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4202 AN: 67964

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0600 Hom.: 235

Bravo AF: 0.0731

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		0.58
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs198545; hg19: chr17-48645611;