rs681271

chr1-181514650-G-Achr1-181514650-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001205293.3(CACNA1E):c.512+3140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,692 control chromosomes in the GnomAD database, including 30,884 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 0.61 (30884 hom., cov: 29)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.512+3140G>A		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.512+3140G>A		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93052 AN: 151574 Hom.: 30848 Cov.: 29

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.614 AC: 93136 AN: 151692 Hom.: 30884 Cov.: 29 AF XY: 0.612 AC XY: 45345 AN XY: 74112

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.611

Alfa AF: 0.512 Hom.: 32621

Bravo AF: 0.630

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	15
Dann	Benign	0.75

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: rs681271; hg19: chr1-181483786;