chr9-137877951-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000718.4(CACNA1B):c.18C>T(p.Asp6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 148,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CACNA1B
NM_000718.4 synonymous
NM_000718.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.732
Genes affected
CACNA1B (HGNC:1389): (calcium voltage-gated channel subunit alpha1 B) The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 9-137877951-C-T is Benign according to our data. Variant chr9-137877951-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1321510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137877951-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.732 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00278 (411/148052) while in subpopulation NFE AF= 0.00408 (271/66490). AF 95% confidence interval is 0.00368. There are 1 homozygotes in gnomad4. There are 208 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 411 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1B | NM_000718.4 | c.18C>T | p.Asp6= | synonymous_variant | 1/47 | ENST00000371372.6 | |
LOC100133077 | NR_121583.1 | n.2692-2271G>A | intron_variant, non_coding_transcript_variant | ||||
CACNA1B | NM_001243812.2 | c.18C>T | p.Asp6= | synonymous_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.18C>T | p.Asp6= | synonymous_variant | 1/47 | 5 | NM_000718.4 | P4 | |
ENST00000371390.1 | n.2692-2271G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00278 AC: 411AN: 147952Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00416 AC: 19AN: 4564Hom.: 0 AF XY: 0.00426 AC XY: 10AN XY: 2348
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00237 AC: 2201AN: 929218Hom.: 0 Cov.: 19 AF XY: 0.00236 AC XY: 1029AN XY: 436632
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | CACNA1B: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2021 | - - |
CACNA1B-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 21, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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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