rs7310552

Positions:

• chr12-47910076-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395324.6(VDR):​c.-83-27302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,096 control chromosomes in the GnomAD database, including 9,018 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (9018 hom., cov: 32)
• Consequence: VDR ENST00000395324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VDR	ENST00000395324.6	c.-83-27302T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46229 AN: 151978 Hom.: 9016 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46244 AN: 152096 Hom.: 9018 Cov.: 32 AF XY: 0.304 AC XY: 22596 AN XY: 74340

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.311

Alfa AF: 0.373 Hom.: 2867

Bravo AF: 0.281

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7310552; hg19: chr12-48303859;