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 (★★).
Verdict is Benign. Variant got -21 ACMG points.
GnomAD3 genomes AF: 0.337AC: 51104AN: 151662Hom.: 9108Cov.: 31 GnomAD3 exomes AF: 0.327AC: 82106AN: 250982Hom.: 14891 AF XY: 0.337AC XY: 45658AN XY: 135678 GnomAD4 exome AF: 0.376AC: 549510AN: 1461414Hom.: 106762 AF XY: 0.376AC XY: 273622AN XY: 727036
Submissions by phenotype
|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||-||- -|
|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, 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. -|
|Likely risk allele, no assertion criteria provided||case-control||Bioengineering and Technology, Gauhati University||Jul 14, 2022||- -|
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