rs7310552

Variant names:

• chr12-47910076-A-G
• rs7310552
• ENST00000395324.6:c.-83-27302T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDR	ENST00000395324.6	TSL:5	c.-83-27302T>C		intron	N/A	ENSP00000378734.2

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

African (AFR) AF: 0.0849 AC: 3524 AN: 41518

American (AMR) AF: 0.307 AC: 4687 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3472

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5178

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4824

European-Finnish (FIN) AF: 0.473 AC: 5008 AN: 10582

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29471 AN: 67932

Other (OTH) AF: 0.311 AC: 657 AN: 2110

Alfa AF: 0.374 Hom.: 4565

Bravo AF: 0.281

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.49
PhyloP100		1.1
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: rs7310552; hg19: chr12-48303859;