chr17-50568250-G-T

Position:

• chr17-50568250-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018896.5(CACNA1G):​c.243-620G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,012 control chromosomes in the GnomAD database, including 487 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 0.072 (487 hom., cov: 32)
• Consequence: CACNA1G NM_018896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.243-620G>T		intron_variant		ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.243-620G>T		intron_variant		1	NM_018896.5	ENSP00000352011	A2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10936 AN: 151894 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0722 AC: 10970 AN: 152012 Hom.: 487 Cov.: 32 AF XY: 0.0713 AC XY: 5301 AN XY: 74318

Gnomad4 AFR AF: 0.0942

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0618

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0584 Hom.: 164

Bravo AF: 0.0731

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.60

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: rs198545; hg19: chr17-48645611;