2-151839245-C-T
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Variant summary
Our verdict is Benign. Variant got -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
NM_000726.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.15
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 Benign. Variant got -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 id is 194344.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNB4 | NM_000726.5 | c.1437G>A | p.Gln479Gln | synonymous_variant | 14/14 | ENST00000539935.7 | NP_000717.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNB4 | ENST00000539935.7 | c.1437G>A | p.Gln479Gln | synonymous_variant | 14/14 | 1 | NM_000726.5 | ENSP00000438949.1 | ||
ENSG00000283228 | ENST00000637559.1 | n.*332+2658G>A | intron_variant | 5 | ENSP00000489697.1 |
Frequencies
GnomAD3 genomes Cov.: 32
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249084Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135130
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461586Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727072
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GnomAD4 genome Cov.: 32
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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
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 14, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 17, 2014 | - - |
Idiopathic generalized epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 14, 2022 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at