rs12073221

Variant names:

• chr1-181444938-G-C
• rs12073221
• ENST00000524607.6:c.434+31358G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CACNA1E Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 69

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.434+31358G>C		intron_variant	Intron 2 of 49		XP_016857732.1
CACNA1E	XM_017002244.2	c.434+31358G>C		intron_variant	Intron 2 of 49		XP_016857733.1
CACNA1E	XM_017002251.1	c.434+31358G>C		intron_variant	Intron 2 of 49		XP_016857740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000524607.6	c.434+31358G>C		intron_variant	Intron 2 of 11	5		ENSP00000432038.2

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

African (AFR) AF: 0.395 AC: 16392 AN: 41448

American (AMR) AF: 0.343 AC: 5234 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3470

East Asian (EAS) AF: 0.140 AC: 722 AN: 5166

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4816

European-Finnish (FIN) AF: 0.319 AC: 3358 AN: 10540

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23458 AN: 67952

Other (OTH) AF: 0.356 AC: 751 AN: 2108

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
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs12073221; hg19: chr1-181414074;