rs117964204

Variant names:

• chr17-50614721-C-T
• rs117964204
• NM_018896.5:c.4760-640C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018896.5(CACNA1G):​c.4760-640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 152,330 control chromosomes in the GnomAD database, including 46 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 0.018 (46 hom., cov: 33)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 16 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=-0.67).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0178 (2704/152330) while in subpopulation NFE AF = 0.0286 (1949/68032). AF 95% confidence interval is 0.0276. There are 46 homozygotes in GnomAd4. There are 1291 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AD,AR gene

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.4760-640C>T		intron	N/A	NP_061496.2
	CACNA1G	NM_198377.3		c.4727-640C>T		intron	N/A	NP_938191.2
	CACNA1G	NM_198396.3		c.4658-640C>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.4760-640C>T		intron	N/A	ENSP00000352011.5
	CACNA1G	ENST00000507336.5	TSL:1	c.4727-640C>T		intron	N/A	ENSP00000420918.1
	CACNA1G	ENST00000507510.6	TSL:1	c.4760-640C>T		intron	N/A	ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2705 AN: 152212 Hom.: 46 Cov.: 33

Gnomad AFR AF: 0.00410

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.00860

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

GnomAD4 genome AF: 0.0178 AC: 2704 AN: 152330 Hom.: 46 Cov.: 33 AF XY: 0.0173 AC XY: 1291 AN XY: 74482

African (AFR) AF: 0.00406 AC: 169 AN: 41584

American (AMR) AF: 0.00725 AC: 111 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.0379 AC: 403 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1949 AN: 68032

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.0247 Hom.: 64

Bravo AF: 0.0147

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.69
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism

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: rs117964204; hg19: chr17-48692082;