rs2184945

Positions:

• chr1-181545790-T-A
• chr1-181545790-T-C
• chr1-181545790-T-G

Variant summary

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

The NM_001205293.3(CACNA1E):​c.513-31976T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,070 control chromosomes in the GnomAD database, including 16,969 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 (16969 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.513-31976T>A		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.513-31976T>A		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68335 AN: 151952 Hom.: 16965 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.449 AC: 68341 AN: 152070 Hom.: 16969 Cov.: 32 AF XY: 0.453 AC XY: 33631 AN XY: 74322

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.482

Alfa AF: 0.497 Hom.: 2471

Bravo AF: 0.434

Asia WGS AF: 0.474 AC: 1649 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	1.5
DANN	Benign	0.35

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: rs2184945; hg19: chr1-181514926;