chr12-47914391-A-G

Variant names:

• chr12-47914391-A-G
• rs7970314
• ENST00000395324.6:c.-84+28472T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395324.6(VDR):​c.-84+28472T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,102 control chromosomes in the GnomAD database, including 18,413 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 0.41 (18413 hom., cov: 31)
• Consequence: VDR ENST00000395324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 20 publications found

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]

VDR Gene-Disease associations (from GenCC):

• vitamin D-dependent rickets, type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• vitamin D-dependent rickets, type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395324.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDR	ENST00000395324.6	TSL:5	c.-84+28472T>C		intron	N/A	ENSP00000378734.2	P11473-1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61604 AN: 151984 Hom.: 18366 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.406 AC: 61691 AN: 152102 Hom.: 18413 Cov.: 31 AF XY: 0.403 AC XY: 29940 AN XY: 74372

African (AFR) AF: 0.833 AC: 34572 AN: 41482

American (AMR) AF: 0.254 AC: 3879 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2852 AN: 5166

South Asian (SAS) AF: 0.413 AC: 1992 AN: 4818

European-Finnish (FIN) AF: 0.169 AC: 1792 AN: 10592

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14569 AN: 67978

Other (OTH) AF: 0.378 AC: 799 AN: 2114

Alfa AF: 0.268 Hom.: 17475

Bravo AF: 0.430

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.42
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7970314; hg19: chr12-48308174;