rs6068816
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000782.5(CYP24A1):c.744G>A(p.Thr248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,614,026 control chromosomes in the GnomAD database, including 12,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.095 ( 1008 hom., cov: 32)
Exomes 𝑓: 0.11 ( 11261 hom. )
Consequence
CYP24A1
NM_000782.5 synonymous
NM_000782.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.32
Genes affected
CYP24A1 (HGNC:2602): (cytochrome P450 family 24 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D3, by hydroxylation of the side chain. In regulating the level of vitamin D3, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [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=-0.63).
BP6
?
Variant 20-54164552-C-T is Benign according to our data. Variant chr20-54164552-C-T is described in ClinVar as [Benign]. Clinvar id is 338825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-54164552-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-4.32 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP24A1 | NM_000782.5 | c.744G>A | p.Thr248= | synonymous_variant | 6/12 | ENST00000216862.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP24A1 | ENST00000216862.8 | c.744G>A | p.Thr248= | synonymous_variant | 6/12 | 1 | NM_000782.5 | P1 | |
CYP24A1 | ENST00000395955.7 | c.744G>A | p.Thr248= | synonymous_variant | 6/11 | 1 | |||
CYP24A1 | ENST00000395954.3 | c.318G>A | p.Thr106= | synonymous_variant | 4/10 | 1 | |||
CYP24A1 | ENST00000487593.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0948 AC: 14411AN: 152056Hom.: 1007 Cov.: 32
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GnomAD3 exomes AF: 0.124 AC: 31139AN: 251404Hom.: 2613 AF XY: 0.126 AC XY: 17137AN XY: 135896
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GnomAD4 exome AF: 0.113 AC: 165407AN: 1461852Hom.: 11261 Cov.: 33 AF XY: 0.115 AC XY: 83343AN XY: 727230
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GnomAD4 genome ? AF: 0.0947 AC: 14415AN: 152174Hom.: 1008 Cov.: 32 AF XY: 0.0958 AC XY: 7129AN XY: 74380
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hypercalcemia, infantile, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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