rs757415

Positions:

• chr17-50587268-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
CACNA1G	NM_018896.5	c.2302-3203C>T		intron_variant		ENST00000359106.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1G	ENST00000359106.10	c.2302-3203C>T		intron_variant		1	NM_018896.5	A2

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

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.435

Alfa AF: 0.415 Hom.: 4193

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs757415; hg19: chr17-48664629;