ENST00000367570:c.-231_-230delTT

Variant names:

• chr1-181483501-CTT-C
• rs111237511
• ENST00000367570:c.-231_-230delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000367570(CACNA1E):​c.-231_-230delTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 208,652 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: 𝑓 0.00033 (0 hom., cov: 29)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: CACNA1E ENST00000367570 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0208 (1446/69444) while in subpopulation EAS AF= 0.0257 (174/6782). AF 95% confidence interval is 0.0225. There are 0 homozygotes in gnomad4_exome. There are 733 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.-243_-242delTT		upstream_gene_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367570	c.-231_-230delTT		5_prime_UTR_variant	Exon 1 of 47	1		ENSP00000356542.1
CACNA1E	ENST00000524607.6	c.435-230_435-229delTT		intron_variant	Intron 2 of 11	5		ENSP00000432038.2
CACNA1E	ENST00000367573.7	c.-243_-242delTT		upstream_gene_variant		1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.-243_-242delTT		upstream_gene_variant		5		ENSP00000353222.3
CACNA1E	ENST00000621791.4	c.-243_-242delTT		upstream_gene_variant		1		ENSP00000481619.1

Frequencies

GnomAD3 genomes AF: 0.000331 AC: 46 AN: 139176 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0208 AC: 1446 AN: 69444 Hom.: 0 AF XY: 0.0203 AC XY: 733 AN XY: 36110

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.0257

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.000330 AC: 46 AN: 139208 Hom.: 0 Cov.: 29 AF XY: 0.000282 AC XY: 19 AN XY: 67454

Gnomad4 AFR AF: 0.00107

Gnomad4 AMR AF: 0.000216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000242

Gnomad4 NFE AF: 0.0000155

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111237511; hg19: chr1-181452637;