rs34503140
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_201596.3(CACNB2):āc.1794T>Cā(p.Ser598=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,613,426 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0085 ( 15 hom., cov: 30)
Exomes š: 0.0035 ( 102 hom. )
Consequence
CACNB2
NM_201596.3 synonymous
NM_201596.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.384
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 10-18539535-T-C is Benign according to our data. Variant chr10-18539535-T-C is described in ClinVar as [Benign]. Clinvar id is 299566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-18539535-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.384 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00852 (1291/151592) while in subpopulation SAS AF= 0.0337 (160/4752). AF 95% confidence interval is 0.0294. There are 15 homozygotes in gnomad4. There are 675 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1291 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1794T>C | p.Ser598= | synonymous_variant | 14/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1632T>C | p.Ser544= | synonymous_variant | 13/13 | ENST00000377329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1794T>C | p.Ser598= | synonymous_variant | 14/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1632T>C | p.Ser544= | synonymous_variant | 13/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.377-236A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00850 AC: 1287AN: 151474Hom.: 15 Cov.: 30
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GnomAD3 exomes AF: 0.00747 AC: 1877AN: 251312Hom.: 36 AF XY: 0.00877 AC XY: 1191AN XY: 135820
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GnomAD4 exome AF: 0.00352 AC: 5143AN: 1461834Hom.: 102 Cov.: 35 AF XY: 0.00446 AC XY: 3241AN XY: 727218
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GnomAD4 genome ? AF: 0.00852 AC: 1291AN: 151592Hom.: 15 Cov.: 30 AF XY: 0.00912 AC XY: 675AN XY: 74046
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Brugada syndrome 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 05, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 07, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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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