rs2280868

Positions:

• chr1-181772675-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001205293.3(CACNA1E):​c.5139+444C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 151,922 control chromosomes in the GnomAD database, including 916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (916 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.5139+444C>A		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.5139+444C>A		intron_variant		1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.5082+444C>A		intron_variant		5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.5139+444C>A		intron_variant		1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.5082+444C>A		intron_variant		1		ENSP00000481619.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15860 AN: 151804 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15857 AN: 151922 Hom.: 916 Cov.: 32 AF XY: 0.106 AC XY: 7837 AN XY: 74226

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.0820

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.110

Alfa AF: 0.116 Hom.: 620

Bravo AF: 0.0988

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -4

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280868; hg19: chr1-181741811;