rs6658713

chr1-181367392-T-C

Variant summary

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

The ENST00000524607.6(CACNA1E):c.-14-45741T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,606 control chromosomes in the GnomAD database, including 8,896 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 0.33 (8896 hom., cov: 31)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	XM_017002243.2	c.-14-45741T>C		intron_variant
CACNA1E	XM_017002244.2	c.-14-45741T>C		intron_variant
CACNA1E	XM_017002245.2	c.-14-45741T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000524607.6	c.-14-45741T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50240 AN: 151492 Hom.: 8864 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.332 AC: 50328 AN: 151606 Hom.: 8896 Cov.: 31 AF XY: 0.326 AC XY: 24179 AN XY: 74132

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.314

Alfa AF: 0.298 Hom.: 11325

Bravo AF: 0.346

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.0
Dann	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6658713; hg19: chr1-181336528;