chr17-50574450-A-G

Variant names:

• chr17-50574450-A-G
• rs198547
• NM_018896.5:c.1141-1093A>G

Variant summary

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

The NM_018896.5(CACNA1G):​c.1141-1093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,284 control chromosomes in the GnomAD database, including 64,413 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 0.92 (64413 hom., cov: 33)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 5 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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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.1141-1093A>G		intron	N/A	NP_061496.2
	CACNA1G	NM_198377.3		c.1141-1093A>G		intron	N/A	NP_938191.2
	CACNA1G	NM_198396.3		c.1141-1093A>G		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.1141-1093A>G		intron	N/A	ENSP00000352011.5
	CACNA1G	ENST00000507336.5	TSL:1	c.1141-1093A>G		intron	N/A	ENSP00000420918.1
	CACNA1G	ENST00000507510.6	TSL:1	c.1141-1093A>G		intron	N/A	ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139787 AN: 152166 Hom.: 64352 Cov.: 33

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.919 AC: 139907 AN: 152284 Hom.: 64413 Cov.: 33 AF XY: 0.920 AC XY: 68499 AN XY: 74454

African (AFR) AF: 0.970 AC: 40331 AN: 41580

American (AMR) AF: 0.933 AC: 14276 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3200 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5045 AN: 5162

South Asian (SAS) AF: 0.917 AC: 4425 AN: 4826

European-Finnish (FIN) AF: 0.893 AC: 9471 AN: 10604

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60194 AN: 68016

Other (OTH) AF: 0.913 AC: 1928 AN: 2112

Alfa AF: 0.895 Hom.: 114197

Bravo AF: 0.925

Asia WGS AF: 0.950 AC: 3305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		-0.67
Mutation Taster		=100/0	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: rs198547; hg19: chr17-48651811;