rs2877651

Positions:

• chr1-181482109-G-A
• chr1-181482109-G-C

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.435-1635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 152,300 control chromosomes in the GnomAD database, including 107 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 0.028 (107 hom., cov: 33)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75

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 (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.435-1635G>A		intron_variant			XP_016857732.1
CACNA1E	XM_017002244.2	c.435-1635G>A		intron_variant			XP_016857733.1
CACNA1E	XM_017002251.1	c.435-1635G>A		intron_variant			XP_016857740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000524607.6	c.435-1635G>A		intron_variant		5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4310 AN: 152182 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0284 AC: 4329 AN: 152300 Hom.: 107 Cov.: 33 AF XY: 0.0284 AC XY: 2114 AN XY: 74474

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0547

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0354

Gnomad4 FIN AF: 0.00442

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0227 Hom.: 37

Bravo AF: 0.0327

Asia WGS AF: 0.0670 AC: 233 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	0.012
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2877651; hg19: chr1-181451245;