rs7976091

Positions:

• chr12-47910769-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000395324.6(VDR):​c.-83-27995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,192 control chromosomes in the GnomAD database, including 16,205 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 0.38 (16205 hom., cov: 33)
• Consequence: VDR ENST00000395324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.47910769C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VDR	ENST00000395324.6	c.-83-27995G>A		intron_variant		5		ENSP00000378734.2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57256 AN: 152074 Hom.: 16169 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.377 AC: 57334 AN: 152192 Hom.: 16205 Cov.: 33 AF XY: 0.372 AC XY: 27661 AN XY: 74394

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.349

Alfa AF: 0.234 Hom.: 1124

Bravo AF: 0.401

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7976091; hg19: chr12-48304552;