rs1999838

chr1-181572217-A-G

Variant summary

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

The NM_001205293.3(CACNA1E):c.513-5549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,928 control chromosomes in the GnomAD database, including 10,693 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 0.37 (10693 hom., cov: 31)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) 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	NM_001205293.3	c.513-5549A>G		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.513-5549A>G		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56489 AN: 151810 Hom.: 10693 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.372 AC: 56496 AN: 151928 Hom.: 10693 Cov.: 31 AF XY: 0.371 AC XY: 27565 AN XY: 74240

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.416

Alfa AF: 0.379 Hom.: 12276

Bravo AF: 0.382

Asia WGS AF: 0.427 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.28
Dann	Benign	0.57

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: rs1999838; hg19: chr1-181541353;