1-181483507-T-TTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000367570.6(CACNA1E):c.-237_-236insCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 344,410 control chromosomes in the GnomAD database, including 349 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (291 hom., cov: 30)
  • Exomes 𝑓: 0.0037 (58 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0920

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 -10 ACMG points.

• BP6: Variant 1-181483507-T-TTC is Benign according to our data. Variant chr1-181483507-T-TTC is described in ClinVar as [Benign]. Clinvar id is 1238863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3			upstream_gene_variant		ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367570.6	c.-237_-236insCT		5_prime_UTR_variant	1/47	1		P4
CACNA1E	ENST00000533229.1	n.198_199insCT		non_coding_transcript_exon_variant	1/7	1
CACNA1E	ENST00000524607.6	c.435-236_435-235insCT		intron_variant		5
CACNA1E	ENST00000367573.7			upstream_gene_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4958 AN: 151264 Hom.: 291 Cov.: 30

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000546

Gnomad OTH AF: 0.0251

GnomAD4 exome AF: 0.00373 AC: 720 AN: 193030 Hom.: 58 Cov.: 0 AF XY: 0.00326 AC XY: 320 AN XY: 98262

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.00872

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000344

Gnomad4 OTH exome AF: 0.00979

GnomAD4 genome AF: 0.0329 AC: 4973 AN: 151380 Hom.: 291 Cov.: 30 AF XY: 0.0322 AC XY: 2382 AN XY: 73994

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000546

Gnomad4 OTH AF: 0.0248

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 28, 2021

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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: rs375048675; hg19: chr1-181452643;