rs33912216
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_172364.5(CACNA2D4):c.3330C>T(p.Gly1110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,612,800 control chromosomes in the GnomAD database, including 8,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 991 hom., cov: 33)
Exomes 𝑓: 0.096 ( 7593 hom. )
Consequence
CACNA2D4
NM_172364.5 synonymous
NM_172364.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.38
Genes affected
CACNA2D4 (HGNC:20202): (calcium voltage-gated channel auxiliary subunit alpha2delta 4) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. 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. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
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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=-0.87).
BP6
?
Variant 12-1793739-G-A is Benign according to our data. Variant chr12-1793739-G-A is described in ClinVar as [Benign]. Clinvar id is 197051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.38 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D4 | NM_172364.5 | c.3330C>T | p.Gly1110= | synonymous_variant | 38/38 | ENST00000382722.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D4 | ENST00000382722.10 | c.3330C>T | p.Gly1110= | synonymous_variant | 38/38 | 1 | NM_172364.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.107 AC: 16322AN: 152152Hom.: 992 Cov.: 33
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GnomAD3 exomes AF: 0.114 AC: 28140AN: 245934Hom.: 2050 AF XY: 0.111 AC XY: 14855AN XY: 134104
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GnomAD4 exome AF: 0.0957 AC: 139733AN: 1460530Hom.: 7593 Cov.: 32 AF XY: 0.0956 AC XY: 69486AN XY: 726606
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GnomAD4 genome ? AF: 0.107 AC: 16334AN: 152270Hom.: 991 Cov.: 33 AF XY: 0.109 AC XY: 8149AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 07, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Retinal cone dystrophy 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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