rs199943

chr1-181629264-C-A

Variant summary

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

The NM_001205293.3(CACNA1E):c.952-22074C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 150,594 control chromosomes in the GnomAD database, including 45,676 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 0.77 (45676 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

Genes affected

CACNA1E (HGNC:1392): (calcium voltage-gated channel subunit alpha1 E) Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These 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 the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.952-22074C>A		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.952-22074C>A		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.774 AC: 116485 AN: 150486 Hom.: 45639 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.774 AC: 116568 AN: 150594 Hom.: 45676 Cov.: 32 AF XY: 0.776 AC XY: 57160 AN XY: 73624

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.774

Alfa AF: 0.808 Hom.: 26618

Bravo AF: 0.759

Asia WGS AF: 0.778 AC: 2695 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.78
Dann	Benign	0.61

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: rs199943; hg19: chr1-181598400;