rs731236
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000376(VDR):c.1056T>C(p.Ile352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151662 control chromosomes in the gnomAD Genomes database, including 9108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (β β ).
Frequency
Genomes: π 0.34 ( 9108 hom., cov: 31)
Exomes π: 0.33 ( 14891 hom. )
Consequence
VDR
NM_000376 synonymous
NM_000376 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.46
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 12:47844974-A>G is Benign according to our data. Variant chr12-47844974-A-G is described in ClinVar as [Benign]. Clinvar id is 308877. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47844974-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.46 with no splicing effect.
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VDR | NM_000376.3 | c.1056T>C | p.Ile352= | synonymous_variant | 10/10 | ENST00000549336.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VDR | ENST00000549336.6 | c.1056T>C | p.Ile352= | synonymous_variant | 10/10 | 1 | NM_000376.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.337 AC: 51104AN: 151662Hom.: 9108 Cov.: 31
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GnomAD3 exomes AF: 0.327 AC: 82106AN: 250982Hom.: 14891 AF XY: 0.337 AC XY: 45658AN XY: 135678
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | p.Ile352Ile in exon 11 of VDR: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 39.88% (26601/66704) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs731236). - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2018 | - - |
Vitamin D-dependent rickets type II with alopecia Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
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. - |
Hepatocellular carcinoma Pathogenic:1
Likely risk allele, no assertion criteria provided | case-control | Bioengineering and Technology, Gauhati University | Jul 14, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out SpliceAI and Pangolin per-transcript scores at