chr1-181483772-G-T

Position:

chr1-181483772-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_ModerateBP6_ModerateBS1BS2

The NM_001205293.3(CACNA1E):c.28G>T(p.Ala10Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,609,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CACNA1E
NM_001205293.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.69

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]

CACNA1E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

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=0.1827536).

BP6

Variant 1-181483772-G-T is Benign according to our data. Variant chr1-181483772-G-T is described in ClinVar as [Benign]. Clinvar id is 1606362.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000725 (11/151756) while in subpopulation AFR AF= 0.000266 (11/41314). AF 95% confidence interval is 0.000149. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1E	NM_001205293.3 linkuse as main transcript	c.28G>T	p.Ala10Ser	missense_variant	1/48	ENST00000367573.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1E	ENST00000367573.7 linkuse as main transcript	c.28G>T	p.Ala10Ser	missense_variant	1/48	1	NM_001205293.3	A2	Q15878-1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134220

show subpopulations

Gnomad AFR exome

AF:

0.0000654

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.00000617

AC:

AN:

1457706

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725038

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151756

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000662

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000166

AC:

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 submitter

clinical testing

Invitae

Jan 03, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.13

.;.;.;.;T;T;.;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;.;.;T;.;T;T;T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

0.95

.;L;L;.;L;.;L;L;L

MutationTaster

Benign

1.0

D;D;D;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.010

.;N;.;N;N;.;.;.;.

REVEL

Benign

0.27

Sift

Benign

0.38

.;T;.;T;T;.;.;.;.

Sift4G

Benign

0.34

.;T;T;T;T;T;T;T;T

Polyphen

0.073

.;B;.;.;.;.;B;.;.

Vest4

0.080, 0.077, 0.13, 0.15, 0.14, 0.12, 0.14, 0.17

MVP

0.76

MPC

0.97

ClinPred

0.10

GERP RS

5.3

Varity_R

0.12

gMVP

0.34

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over