chr1-181483501-C-CT

Position:

• chr1-181483501-C-CT

Variant summary

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

The ENST00000367570.6(CACNA1E):​c.-230dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 210,186 control chromosomes in the GnomAD database, including 62 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (62 hom., cov: 29)
  • Exomes 𝑓: 0.057 (0 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 1-181483501-C-CT is Benign according to our data. Variant chr1-181483501-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1300505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 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.-230dup		5_prime_UTR_variant	1/47	1		P4
CACNA1E	ENST00000533229.1	n.205dup		non_coding_transcript_exon_variant	1/7	1
CACNA1E	ENST00000524607.6	c.435-229dup		intron_variant		5
CACNA1E	ENST00000367573.7			upstream_gene_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3516 AN: 139134 Hom.: 62 Cov.: 29

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.0365

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0284

Gnomad EAS AF: 0.00601

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0185

GnomAD4 exome AF: 0.0566 AC: 4019 AN: 71020 Hom.: 0 Cov.: 0 AF XY: 0.0574 AC XY: 2118 AN XY: 36896

Gnomad4 AFR exome AF: 0.0647

Gnomad4 AMR exome AF: 0.0568

Gnomad4 ASJ exome AF: 0.0752

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.0582

GnomAD4 genome AF: 0.0253 AC: 3522 AN: 139166 Hom.: 62 Cov.: 29 AF XY: 0.0246 AC XY: 1660 AN XY: 67432

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0284

Gnomad4 EAS AF: 0.00582

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0184

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 23, 2021

- -

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;