rs12071300

Variant names:

• chr1-181629953-T-G
• rs12071300
• NM_001205293.3:c.952-21385T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205293.3(CACNA1E):​c.952-21385T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,980 control chromosomes in the GnomAD database, including 3,090 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 0.19 (3090 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.952-21385T>G		intron_variant	Intron 6 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.952-21385T>G		intron_variant	Intron 6 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.952-21385T>G		intron_variant	Intron 6 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.952-21385T>G		intron_variant	Intron 6 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.952-21385T>G		intron_variant	Intron 6 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.1387-21385T>G		intron_variant	Intron 8 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29005 AN: 151862 Hom.: 3089 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.191 AC: 29010 AN: 151980 Hom.: 3090 Cov.: 32 AF XY: 0.190 AC XY: 14116 AN XY: 74306

African (AFR) AF: 0.253 AC: 10475 AN: 41396

American (AMR) AF: 0.184 AC: 2815 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3470

East Asian (EAS) AF: 0.0589 AC: 305 AN: 5176

South Asian (SAS) AF: 0.350 AC: 1689 AN: 4822

European-Finnish (FIN) AF: 0.122 AC: 1289 AN: 10582

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11190 AN: 67948

Other (OTH) AF: 0.193 AC: 407 AN: 2106

Alfa AF: 0.182 Hom.: 1418

Bravo AF: 0.192

Asia WGS AF: 0.212 AC: 739 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	11
DANN	Benign	0.72
PhyloP100		-0.081
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12071300; hg19: chr1-181599089;