17-50574450-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.1141-1093A>G		intron_variant	Intron 7 of 37	ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.1141-1093A>G		intron_variant	Intron 7 of 37	1	NM_018896.5	ENSP00000352011.5
CACNA1G	ENST00000507510.6	c.1141-1093A>G		intron_variant	Intron 7 of 36	1		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

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.933

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.913

Alfa AF: 0.893 Hom.: 81419

Bravo AF: 0.925

Asia WGS AF: 0.950 AC: 3305 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	11
DANN	Benign	0.84

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: rs198547; hg19: chr17-48651811;