rs704331

Positions:

• chr1-181755073-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000367573.7(CACNA1E):​c.3829-164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,942 control chromosomes in the GnomAD database, including 12,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12719 hom., cov: 31)
• Consequence: CACNA1E ENST00000367573.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.377

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=-0.85).
• BP6: Variant 1-181755073-A-G is Benign according to our data. Variant chr1-181755073-A-G is described in ClinVar as [Benign]. Clinvar id is 1257674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.3829-164A>G		intron_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.3829-164A>G		intron_variant		1	NM_001205293.3	ENSP00000356545	A2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58143 AN: 151824 Hom.: 12706 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.383 AC: 58181 AN: 151942 Hom.: 12719 Cov.: 31 AF XY: 0.384 AC XY: 28468 AN XY: 74226

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.377

Alfa AF: 0.426 Hom.: 3065

Bravo AF: 0.358

Asia WGS AF: 0.300 AC: 1046 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 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.78

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: rs704331; hg19: chr1-181724209;