chr12-47844438-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000376.3(VDR):c.*308C>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 0.52 in 539,752 control chromosomes in the GnomAD database, including 74,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.53 ( 21596 hom., cov: 33)
Exomes 𝑓: 0.52 ( 52968 hom. )
Consequence
VDR
NM_000376.3 3_prime_UTR
NM_000376.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.58
Genes affected
VDR (HGNC:12679): (vitamin D receptor) This gene encodes vitamin D3 receptor, which is a member of the nuclear hormone receptor superfamily of ligand-inducible transcription factors. This receptor also functions as a receptor for the secondary bile acid, lithocholic acid. Downstream targets of vitamin D3 receptor are principally involved in mineral metabolism, though this receptor regulates a variety of other metabolic pathways, such as those involved in immune response and cancer. Mutations in this gene are associated with type II vitamin D-resistant rickets. A single nucleotide polymorphism in the initiation codon results in an alternate translation start site three codons downstream. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Jun 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 12-47844438-G-T is Benign according to our data. Variant chr12-47844438-G-T is described in ClinVar as [Benign]. Clinvar id is 308868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VDR | NM_000376.3 | c.*308C>A | 3_prime_UTR_variant | 10/10 | ENST00000549336.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VDR | ENST00000549336.6 | c.*308C>A | 3_prime_UTR_variant | 10/10 | 1 | NM_000376.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.530 AC: 80505AN: 151978Hom.: 21577 Cov.: 33
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GnomAD4 exome AF: 0.517 AC: 200273AN: 387656Hom.: 52968 Cov.: 2 AF XY: 0.519 AC XY: 105533AN XY: 203216
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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:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2018 | This variant is associated with the following publications: (PMID: 29241179) - |
Vitamin D-dependent rickets type II with alopecia 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. - |
Periodontitis Benign:1
Benign, no assertion criteria provided | case-control | Genetics Laboratory, Lanzhou University | Apr 20, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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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