rs777607595
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_201596.3(CACNB2):c.1833C>T(p.Asp611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,406 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
CACNB2
NM_201596.3 synonymous
NM_201596.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.96
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 10-18539574-C-T is Benign according to our data. Variant chr10-18539574-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 416841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.96 with no splicing effect.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB2 | NM_201596.3 | c.1833C>T | p.Asp611= | synonymous_variant | 14/14 | ENST00000324631.13 | |
CACNB2 | NM_201590.3 | c.1671C>T | p.Asp557= | synonymous_variant | 13/13 | ENST00000377329.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB2 | ENST00000324631.13 | c.1833C>T | p.Asp611= | synonymous_variant | 14/14 | 1 | NM_201596.3 | ||
CACNB2 | ENST00000377329.10 | c.1671C>T | p.Asp557= | synonymous_variant | 13/13 | 1 | NM_201590.3 | ||
ENST00000425669.1 | n.377-275G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000330 AC: 5AN: 151548Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251230Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135766
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461858Hom.: 0 Cov.: 35 AF XY: 0.0000289 AC XY: 21AN XY: 727228
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GnomAD4 genome ? AF: 0.0000330 AC: 5AN: 151548Hom.: 0 Cov.: 30 AF XY: 0.0000271 AC XY: 2AN XY: 73932
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Brugada syndrome 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 31, 2019 | This alteration is classified as likely 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