rs2609473

Positions:

• chr1-181366371-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000524607.6(CACNA1E):​c.-14-46762G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,036 control chromosomes in the GnomAD database, including 24,964 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 0.57 (24964 hom., cov: 32)
• Consequence: CACNA1E ENST00000524607.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	XM_017002243.2	c.-14-46762G>T		intron_variant			XP_016857732.1
CACNA1E	XM_017002244.2	c.-14-46762G>T		intron_variant			XP_016857733.1
CACNA1E	XM_017002245.2	c.-14-46762G>T		intron_variant			XP_016857734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000524607.6	c.-14-46762G>T		intron_variant		5		ENSP00000432038

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86217 AN: 151918 Hom.: 24928 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.568 AC: 86308 AN: 152036 Hom.: 24964 Cov.: 32 AF XY: 0.563 AC XY: 41840 AN XY: 74296

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.516

Alfa AF: 0.538 Hom.: 30074

Bravo AF: 0.577

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2609473; hg19: chr1-181335507;