chr1-181772165-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000367573.7(CACNA1E):​c.5073C>G​(p.Asn1691Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1691S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

CACNA1E
ENST00000367573.7 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CACNA1E. . Gene score misZ 5.8125 (greater than the threshold 3.09). Trascript score misZ 6.7013 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, developmental and epileptic encephalopathy, 69.
BP4
Computational evidence support a benign effect (MetaRNN=0.2511331).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1ENM_001205293.3 linkuse as main transcriptc.5073C>G p.Asn1691Lys missense_variant 37/48 ENST00000367573.7 NP_001192222.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1EENST00000367573.7 linkuse as main transcriptc.5073C>G p.Asn1691Lys missense_variant 37/481 NM_001205293.3 ENSP00000356545 A2Q15878-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
0.017
DANN
Benign
0.95
DEOGEN2
Uncertain
0.49
.;.;.;T;T;.;T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.83
.;.;T;.;T;T;T;T
M_CAP
Benign
0.083
D
MetaRNN
Benign
0.25
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
0.13
N;.;.;N;.;N;N;.
MutationTaster
Benign
0.42
P;P;P;P;P;P;P
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.68
N;.;N;N;.;.;.;.
REVEL
Uncertain
0.39
Sift
Benign
0.71
T;.;T;T;.;.;.;.
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T
Polyphen
0.0020
B;B;.;B;.;B;B;B
Vest4
0.14
MutPred
0.52
Gain of methylation at N1691 (P = 0.0011);.;.;Gain of methylation at N1691 (P = 0.0011);.;Gain of methylation at N1691 (P = 0.0011);Gain of methylation at N1691 (P = 0.0011);.;
MVP
0.67
MPC
1.5
ClinPred
0.13
T
GERP RS
-5.5
Varity_R
0.049
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs199930; hg19: chr1-181741301; API