1-181575901-G-T

Variant names:

• chr1-181575901-G-T
• rs7511748
• NM_001205293.3:c.513-1865G>T

Variant summary

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

The NM_001205293.3(CACNA1E):​c.513-1865G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,768 control chromosomes in the GnomAD database, including 25,622 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 0.58 (25622 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 2 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: Illumina, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	NM_001205293.3	MANE Select	c.513-1865G>T		intron	N/A	NP_001192222.1	Q15878-1
	CACNA1E	NM_000721.4		c.513-1865G>T		intron	N/A	NP_000712.2	Q15878-3
	CACNA1E	NM_001205294.2		c.513-1865G>T		intron	N/A	NP_001192223.1	Q15878-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367573.7	TSL:1 MANE Select	c.513-1865G>T		intron	N/A	ENSP00000356545.2	Q15878-1
	CACNA1E	ENST00000360108.7	TSL:5	c.513-1865G>T		intron	N/A	ENSP00000353222.3	F8W9Z1
	CACNA1E	ENST00000367570.6	TSL:1	c.513-1865G>T		intron	N/A	ENSP00000356542.1	Q15878-3

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87662 AN: 151650 Hom.: 25591 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.578 AC: 87744 AN: 151768 Hom.: 25622 Cov.: 32 AF XY: 0.583 AC XY: 43253 AN XY: 74180

African (AFR) AF: 0.532 AC: 21972 AN: 41338

American (AMR) AF: 0.555 AC: 8469 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3609 AN: 5170

South Asian (SAS) AF: 0.595 AC: 2872 AN: 4824

European-Finnish (FIN) AF: 0.585 AC: 6173 AN: 10548

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40440 AN: 67850

Other (OTH) AF: 0.551 AC: 1161 AN: 2108

Alfa AF: 0.581 Hom.: 54579

Bravo AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.48
DANN	Benign	0.48
PhyloP100		-0.77
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: rs7511748; hg19: chr1-181545037;