rs757415

Variant names:

• chr17-50587268-C-T
• rs757415
• NM_018896.5:c.2302-3203C>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.2302-3203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,952 control chromosomes in the GnomAD database, including 16,562 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 0.45 (16562 hom., cov: 31)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• 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 = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.2302-3203C>T		intron_variant	Intron 9 of 37	ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.2302-3203C>T		intron_variant	Intron 9 of 37	1	NM_018896.5	ENSP00000352011.5
CACNA1G	ENST00000507510.6	c.2302-3203C>T		intron_variant	Intron 9 of 36	1		ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68696 AN: 151834 Hom.: 16553 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.452 AC: 68733 AN: 151952 Hom.: 16562 Cov.: 31 AF XY: 0.461 AC XY: 34258 AN XY: 74276

African (AFR) AF: 0.515 AC: 21330 AN: 41408

American (AMR) AF: 0.475 AC: 7263 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4580 AN: 5162

South Asian (SAS) AF: 0.606 AC: 2918 AN: 4814

European-Finnish (FIN) AF: 0.438 AC: 4628 AN: 10560

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25325 AN: 67950

Other (OTH) AF: 0.435 AC: 917 AN: 2106

Alfa AF: 0.413 Hom.: 5272

Bravo AF: 0.457

Asia WGS AF: 0.697 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.6
DANN	Benign	0.91
PhyloP100		-0.28
Mutation Taster		=99/1	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: rs757415; hg19: chr17-48664629;