rs12073221

Positions:

• chr1-181444938-G-C
• chr1-181444938-G-T

Variant summary

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

The ENST00000524607.6(CACNA1E):​c.434+31358G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,984 control chromosomes in the GnomAD database, including 9,381 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 0.35 (9381 hom., cov: 32)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	XM_017002243.2	c.434+31358G>C		intron_variant
CACNA1E	XM_017002244.2	c.434+31358G>C		intron_variant
CACNA1E	XM_017002245.2	c.434+31358G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000524607.6	c.434+31358G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52782 AN: 151866 Hom.: 9380 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.347 AC: 52811 AN: 151984 Hom.: 9381 Cov.: 32 AF XY: 0.345 AC XY: 25617 AN XY: 74296

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.356

Alfa AF: 0.223 Hom.: 491

Bravo AF: 0.351

Asia WGS AF: 0.227 AC: 792 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12073221; hg19: chr1-181414074;