rs797045425

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000726.5(CACNB4):​c.50C>T​(p.Ser17Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,372,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S17C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

CACNB4
NM_000726.5 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.26
Variant links:
Genes affected
CACNB4 (HGNC:1404): (calcium voltage-gated channel auxiliary subunit beta 4) This gene encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein encoded by this locus plays an important role in calcium channel function by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE), juvenile myoclonic epilepsy (JME), and episodic ataxia, type 5. [provided by RefSeq, Aug 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.236321).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNB4NM_000726.5 linkuse as main transcriptc.50C>T p.Ser17Phe missense_variant 1/14 ENST00000539935.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNB4ENST00000539935.7 linkuse as main transcriptc.50C>T p.Ser17Phe missense_variant 1/141 NM_000726.5 O00305-1
ENST00000420365.1 linkuse as main transcriptn.120+515G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.29e-7
AC:
1
AN:
1372278
Hom.:
0
Cov.:
30
AF XY:
0.00000148
AC XY:
1
AN XY:
676482
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.35e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Benign
0.95
DEOGEN2
Benign
0.12
T;.;.;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.80
T;T;T;T
M_CAP
Pathogenic
0.34
D
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
0.34
N;.;.;N
MutationTaster
Benign
0.70
D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.92
N;.;.;N
REVEL
Uncertain
0.38
Sift
Uncertain
0.0050
D;.;.;D
Sift4G
Uncertain
0.025
D;.;.;D
Polyphen
0.19
B;.;.;.
Vest4
0.46
MutPred
0.20
Loss of glycosylation at S17 (P = 0.0059);Loss of glycosylation at S17 (P = 0.0059);Loss of glycosylation at S17 (P = 0.0059);Loss of glycosylation at S17 (P = 0.0059);
MVP
0.83
MPC
0.79
ClinPred
0.65
D
GERP RS
3.7
Varity_R
0.26
gMVP
0.34

Splicing

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: rs797045425; hg19: chr2-152955476; API