chr1-181686616-C-T

Variant names:

• chr1-181686616-C-T
• rs3845441
• NM_001205293.3:c.1056-24338C>T

Variant summary

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

The NM_001205293.3(CACNA1E):​c.1056-24338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,166 control chromosomes in the GnomAD database, including 53,598 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 0.84 (53598 hom., cov: 31)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.1056-24338C>T		intron_variant	Intron 7 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.1056-24338C>T		intron_variant	Intron 7 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.1056-24338C>T		intron_variant	Intron 7 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.1056-24338C>T		intron_variant	Intron 7 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.1056-24338C>T		intron_variant	Intron 7 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.1491-24338C>T		intron_variant	Intron 9 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127521 AN: 152048 Hom.: 53550 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.839 AC: 127625 AN: 152166 Hom.: 53598 Cov.: 31 AF XY: 0.842 AC XY: 62606 AN XY: 74396

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.808

Alfa AF: 0.833 Hom.: 3824

Bravo AF: 0.834

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.056
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3845441; hg19: chr1-181655752;