rs16857509

chr1-181525639-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.512+14129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,190 control chromosomes in the GnomAD database, including 1,349 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 0.13 (1349 hom., cov: 33)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3	c.512+14129A>G		intron_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7	c.512+14129A>G		intron_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19363 AN: 152072 Hom.: 1351 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.127 AC: 19364 AN: 152190 Hom.: 1349 Cov.: 33 AF XY: 0.129 AC XY: 9585 AN XY: 74398

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.126

Alfa AF: 0.133 Hom.: 1845

Bravo AF: 0.123

Asia WGS AF: 0.0840 AC: 295 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.62

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: rs16857509; hg19: chr1-181494775;