rs2041139
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_172364.5(CACNA2D4):c.*1360G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,280 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.027 ( 109 hom., cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CACNA2D4
NM_172364.5 3_prime_UTR
NM_172364.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.96
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 12-1792295-C-T is Benign according to our data. Variant chr12-1792295-C-T is described in ClinVar as [Benign]. Clinvar id is 307805.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D4 | NM_172364.5 | c.*1360G>A | 3_prime_UTR_variant | 38/38 | ENST00000382722.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D4 | ENST00000382722.10 | c.*1360G>A | 3_prime_UTR_variant | 38/38 | 1 | NM_172364.5 | P2 | ||
CACNA2D4 | ENST00000537784.5 | c.*1967G>A | 3_prime_UTR_variant, NMD_transcript_variant | 15/15 | 1 | ||||
CACNA2D4 | ENST00000280663.12 | n.5604G>A | non_coding_transcript_exon_variant | 36/36 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0264 AC: 4021AN: 152162Hom.: 109 Cov.: 34
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 12Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 6
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GnomAD4 genome ? AF: 0.0265 AC: 4043AN: 152280Hom.: 109 Cov.: 34 AF XY: 0.0298 AC XY: 2219AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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. - |
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