chr1-181636029-A-G

Variant names:

• chr1-181636029-A-G
• rs175338
• NM_001205293.3:c.952-15309A>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.952-15309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,136 control chromosomes in the GnomAD database, including 38,988 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 0.70 (38988 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.952-15309A>G		intron	N/A	NP_001192222.1
	CACNA1E	NM_000721.4		c.952-15309A>G		intron	N/A	NP_000712.2
	CACNA1E	NM_001205294.2		c.952-15309A>G		intron	N/A	NP_001192223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.952-15309A>G		intron	N/A	ENSP00000356545.2
	CACNA1E	ENST00000360108.7	TSL:5	c.952-15309A>G		intron	N/A	ENSP00000353222.3
	CACNA1E	ENST00000367570.6	TSL:1	c.952-15309A>G		intron	N/A	ENSP00000356542.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106505 AN: 152018 Hom.: 38960 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.701 AC: 106576 AN: 152136 Hom.: 38988 Cov.: 32 AF XY: 0.704 AC XY: 52336 AN XY: 74378

African (AFR) AF: 0.485 AC: 20132 AN: 41488

American (AMR) AF: 0.762 AC: 11643 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2899 AN: 3468

East Asian (EAS) AF: 0.940 AC: 4878 AN: 5188

South Asian (SAS) AF: 0.613 AC: 2956 AN: 4820

European-Finnish (FIN) AF: 0.803 AC: 8501 AN: 10582

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53156 AN: 67988

Other (OTH) AF: 0.737 AC: 1557 AN: 2112

Alfa AF: 0.757 Hom.: 55077

Bravo AF: 0.694

Asia WGS AF: 0.760 AC: 2639 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		0.22
Mutation Taster		=100/0	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: rs175338; hg19: chr1-181605165;