rs147857449
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_201596.3(CACNB2):c.1206+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,608,896 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0054 ( 9 hom., cov: 33)
Exomes 𝑓: 0.00063 ( 8 hom. )
Consequence
CACNB2
NM_201596.3 splice_donor_region, intron
NM_201596.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.004505
2
Clinical Significance
Conservation
PhyloP100: -0.157
Genes affected
CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 10-18534233-T-C is Benign according to our data. Variant chr10-18534233-T-C is described in ClinVar as [Benign]. Clinvar id is 299560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-18534233-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00536 (816/152342) while in subpopulation AFR AF= 0.0183 (760/41574). AF 95% confidence interval is 0.0172. There are 9 homozygotes in gnomad4. There are 386 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 814 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201590.3 | c.1044+6T>C | splice_donor_region_variant, intron_variant | ENST00000377329.10 | |||
CACNB2 | NM_201596.3 | c.1206+6T>C | splice_donor_region_variant, intron_variant | ENST00000324631.13 | |||
LOC124902387 | XR_007062077.1 | n.564A>G | non_coding_transcript_exon_variant | 1/2 | |||
LOC124902386 | XR_007062076.1 | n.83+4961A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1206+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_201596.3 | ||||
CACNB2 | ENST00000377329.10 | c.1044+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_201590.3 | ||||
ENST00000425669.1 | n.482+4961A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00535 AC: 814AN: 152224Hom.: 9 Cov.: 33
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GnomAD3 exomes AF: 0.00151 AC: 379AN: 251214Hom.: 4 AF XY: 0.00117 AC XY: 159AN XY: 135808
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GnomAD4 exome AF: 0.000633 AC: 922AN: 1456554Hom.: 8 Cov.: 29 AF XY: 0.000603 AC XY: 437AN XY: 725036
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Brugada syndrome 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 20, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at