Variant rs797045425 details in Genebe, Genetics Data Aggregator

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

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]

CACNB4 links:

(HGNC:):

links:

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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
CACNB4	NM_000726.5 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	1/14	ENST00000539935.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB4	ENST00000539935.7 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	1/14	1	NM_000726.5		O00305-1
	ENST00000420365.1 linkuse as main transcript	n.120+515G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.29e-7

AC:

AN:

1372278

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.12

T;.;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.34

N;.;.;N

MutationTaster

Benign

0.70

D;D;D

PrimateAI

Uncertain

0.74

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over