rs2280866

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001205293.3(CACNA1E):​c.3423-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,317,528 control chromosomes in the GnomAD database, including 114,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 10880 hom., cov: 33)
Exomes 𝑓: 0.42 ( 104066 hom. )

Consequence

CACNA1E
NM_001205293.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 1-181737416-G-A is Benign according to our data. Variant chr1-181737416-G-A is described in ClinVar as [Benign]. Clinvar id is 1260688.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA1ENM_001205293.3 linkuse as main transcriptc.3423-109G>A intron_variant ENST00000367573.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA1EENST00000367573.7 linkuse as main transcriptc.3423-109G>A intron_variant 1 NM_001205293.3 A2Q15878-1

Frequencies

GnomAD3 genomes
AF:
0.369
AC:
56012
AN:
151946
Hom.:
10861
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.279
Gnomad AMI
AF:
0.414
Gnomad AMR
AF:
0.316
Gnomad ASJ
AF:
0.428
Gnomad EAS
AF:
0.249
Gnomad SAS
AF:
0.255
Gnomad FIN
AF:
0.397
Gnomad MID
AF:
0.361
Gnomad NFE
AF:
0.445
Gnomad OTH
AF:
0.352
GnomAD4 exome
AF:
0.417
AC:
486471
AN:
1165466
Hom.:
104066
AF XY:
0.414
AC XY:
238337
AN XY:
576024
show subpopulations
Gnomad4 AFR exome
AF:
0.270
Gnomad4 AMR exome
AF:
0.252
Gnomad4 ASJ exome
AF:
0.413
Gnomad4 EAS exome
AF:
0.277
Gnomad4 SAS exome
AF:
0.267
Gnomad4 FIN exome
AF:
0.405
Gnomad4 NFE exome
AF:
0.446
Gnomad4 OTH exome
AF:
0.390
GnomAD4 genome
AF:
0.369
AC:
56070
AN:
152062
Hom.:
10880
Cov.:
33
AF XY:
0.364
AC XY:
27047
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.279
Gnomad4 AMR
AF:
0.316
Gnomad4 ASJ
AF:
0.428
Gnomad4 EAS
AF:
0.250
Gnomad4 SAS
AF:
0.255
Gnomad4 FIN
AF:
0.397
Gnomad4 NFE
AF:
0.445
Gnomad4 OTH
AF:
0.357
Alfa
AF:
0.387
Hom.:
2316
Bravo
AF:
0.357
Asia WGS
AF:
0.264
AC:
922
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 11, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
13
DANN
Benign
0.81

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2280866; hg19: chr1-181706552; COSMIC: COSV62385094; API