1-181483507-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000367570.6(CACNA1E):c.-238T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 344,416 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (44 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-181483507-T-C is Benign according to our data. Variant chr1-181483507-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1300371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1974/151380) while in subpopulation AFR AF= 0.0447 (1840/41146). AF 95% confidence interval is 0.043. There are 44 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1970 AD gene.

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.-238T>C		5_prime_UTR_variant	1/47	1		P4
CACNA1E	ENST00000533229.1	n.197T>C		non_coding_transcript_exon_variant	1/7	1
CACNA1E	ENST00000524607.6	c.435-237T>C		intron_variant		5
CACNA1E	ENST00000367573.7			upstream_gene_variant		1	NM_001205293.3	A2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1970 AN: 151264 Hom.: 43 Cov.: 31

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00604

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.0106

GnomAD4 exome AF: 0.00141 AC: 272 AN: 193036 Hom.: 9 Cov.: 0 AF XY: 0.00116 AC XY: 114 AN XY: 98264

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.00262

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: 0.000176

Gnomad4 OTH exome AF: 0.00370

GnomAD4 genome AF: 0.0130 AC: 1974 AN: 151380 Hom.: 44 Cov.: 31 AF XY: 0.0123 AC XY: 907 AN XY: 73996

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.00604

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.0146 Hom.: 4

Bravo AF: 0.0151

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 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.097
Dann	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111830180; hg19: chr1-181452643;