NM_000726.5:c.1411_1413delAGGinsCGC

Variant names:

• chr2-151839269-CCT-GCG
• NM_000726.5:c.1411_1413delAGGinsCGC
• CACNB4 p.472

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000726.5(CACNB4):​c.1411_1413delAGGinsCGC​(p.472) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R471R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNB4 NM_000726.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), G2P
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000283228 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000726.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB4	NM_000726.5	MANE Select	c.1411_1413delAGGinsCGC	p.472	synonymous	N/A	NP_000717.2	O00305-1
	CACNB4	NM_001005746.4		c.1357_1359delAGGinsCGC	p.454	synonymous	N/A	NP_001005746.1	O00305-3
	CACNB4	NM_001005747.4		c.1309_1311delAGGinsCGC	p.438	synonymous	N/A	NP_001005747.1	O00305-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB4	ENST00000539935.7	TSL:1 MANE Select	c.1411_1413delAGGinsCGC	p.472	synonymous	N/A	ENSP00000438949.1	O00305-1
	CACNB4	ENST00000534999.7	TSL:1	c.1309_1311delAGGinsCGC	p.438	synonymous	N/A	ENSP00000443893.1	O00305-2
	CACNB4	ENST00000201943.10	TSL:1	c.1225_1227delAGGinsCGC	p.410	synonymous	N/A	ENSP00000201943.5	O00305-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-152695783;