rs794727118

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_000726.5(CACNB4):c.1437G>A(p.Gln479Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CACNB4
NM_000726.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.15

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

episodic ataxia type 5
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
juvenile myoclonic epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, idiopathic generalized, susceptibility to, 9
Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CACNB4 links:

ENSG00000283228 (HGNC:):

ENSG00000283228 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-151839245-C-T is Benign according to our data. Variant chr2-151839245-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 194344.

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB4	NM_000726.5 link	c.1437G>A	p.Gln479Gln	synonymous_variant	Exon 14 of 14	ENST00000539935.7	NP_000717.2	O00305-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB4	ENST00000539935.7 link	c.1437G>A	p.Gln479Gln	synonymous_variant	Exon 14 of 14	1	NM_000726.5	ENSP00000438949.1		O00305-1
ENSG00000283228	ENST00000637559.1 link	n.*332+2658G>A		intron_variant	Intron 10 of 11	5		ENSP00000489697.1		A0A1B0GTH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

249084

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111778

Other (OTH)

AF:

0.0000497

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Sep 14, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 17, 2014

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Idiopathic generalized epilepsy

Benign:1

Jun 14, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

5.6

(source)

DANN

Benign

0.67

PhyloP100

1.2

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over