1-181483212-CTTTG-C

Position:

• chr1-181483212-CTTTG-C

Variant summary

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

The ENST00000367570.6(CACNA1E):​c.-529_-526del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,098 control chromosomes in the GnomAD database, including 1,251 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1251 hom., cov: 30)
  • Exomes 𝑓: 0.088 (0 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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 1-181483212-CTTTG-C is Benign according to our data. Variant chr1-181483212-CTTTG-C is described in ClinVar as [Benign]. Clinvar id is 1273449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.435-528_435-525del		intron_variant			XP_016857732.1
CACNA1E	XM_017002244.2	c.435-528_435-525del		intron_variant			XP_016857733.1
CACNA1E	XM_017002245.2	c.435-528_435-525del		intron_variant			XP_016857734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367570.6	c.-529_-526del		5_prime_UTR_variant	1/47	1		ENSP00000356542	P4
CACNA1E	ENST00000524607.6	c.435-528_435-525del		intron_variant		5		ENSP00000432038

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19111 AN: 151912 Hom.: 1249 Cov.: 30

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.0882 AC: 6 AN: 68 Hom.: 0 AF XY: 0.0750 AC XY: 3 AN XY: 40

Gnomad4 AFR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0588

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.126 AC: 19111 AN: 152030 Hom.: 1251 Cov.: 30 AF XY: 0.121 AC XY: 8976 AN XY: 74310

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.0592

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.132

Alfa AF: 0.138 Hom.: 181

Bravo AF: 0.127

Asia WGS AF: 0.0790 AC: 274 AN: 3478

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 26, 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: rs5779103; hg19: chr1-181452348;