12-47845054-C-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000376.3(VDR):c.1025-49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,600,160 control chromosomes in the GnomAD database, including 225,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.55 ( 23205 hom., cov: 29)
Exomes 𝑓: 0.53 ( 202307 hom. )
Consequence
VDR
NM_000376.3 intron
NM_000376.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.874
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=-0.78).
BP6
?
Variant 12-47845054-C-A is Benign according to our data. Variant chr12-47845054-C-A is described in ClinVar as [Benign]. Clinvar id is 1252227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VDR | NM_000376.3 | c.1025-49G>T | intron_variant | ENST00000549336.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VDR | ENST00000549336.6 | c.1025-49G>T | intron_variant | 1 | NM_000376.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.549 AC: 82955AN: 151104Hom.: 23182 Cov.: 29
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GnomAD3 exomes AF: 0.511 AC: 123050AN: 240798Hom.: 32488 AF XY: 0.518 AC XY: 67861AN XY: 130972
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GnomAD4 exome AF: 0.525 AC: 761265AN: 1448938Hom.: 202307 Cov.: 47 AF XY: 0.528 AC XY: 380601AN XY: 721232
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GnomAD4 genome ? AF: 0.549 AC: 83031AN: 151222Hom.: 23205 Cov.: 29 AF XY: 0.549 AC XY: 40532AN XY: 73840
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hepatocellular carcinoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | case-control | Bioengineering and Technology, Gauhati University | Jul 14, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2018 | - - |
Vitamin D-dependent rickets type II with alopecia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Periodontitis Benign:1
Benign, no assertion criteria provided | case-control | Genetics Laboratory, Lanzhou University | Apr 20, 2023 | - - |
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