ENST00000367570.6:c.-238_-230delTTTTTTTTT

Variant names:

• chr1-181483501-CTTTTTTTTT-C
• rs111237511
• ENST00000367570.6:c.-238_-230delTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000367570.6(CACNA1E):​c.-238_-230delTTTTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 71,606 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367570.6. 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.-243_-235delTTTTTTTTT		upstream_gene	N/A	NP_001192222.1	Q15878-1
	CACNA1E	NM_000721.4		c.-243_-235delTTTTTTTTT		upstream_gene	N/A	NP_000712.2	Q15878-3
	CACNA1E	NM_001205294.2		c.-243_-235delTTTTTTTTT		upstream_gene	N/A	NP_001192223.1	Q15878-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1E	ENST00000367570.6	TSL:1	c.-238_-230delTTTTTTTTT		5_prime_UTR	Exon 1 of 47	ENSP00000356542.1	Q15878-3
	CACNA1E	ENST00000524607.6	TSL:5	c.435-237_435-229delTTTTTTTTT		intron	N/A	ENSP00000432038.2	E9PIE8
	CACNA1E	ENST00000533229.1	TSL:1	n.197_205delTTTTTTTTT		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000140 AC: 1 AN: 71606 Hom.: 0 AF XY: 0.0000269 AC XY: 1 AN XY: 37240

African (AFR) AF: 0.00 AC: 0 AN: 2064

American (AMR) AF: 0.00 AC: 0 AN: 2164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2544

East Asian (EAS) AF: 0.000143 AC: 1 AN: 6984

South Asian (SAS) AF: 0.00 AC: 0 AN: 1458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46876

Other (OTH) AF: 0.00 AC: 0 AN: 4728

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs111237511; hg19: chr1-181452637;