rs7302038

Variant names:

• chr12-47913858-G-A
• rs7302038
• ENST00000395324.6:c.-84+29005C>T

Variant summary

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

The ENST00000395324.6(VDR):​c.-84+29005C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,074 control chromosomes in the GnomAD database, including 4,224 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 0.13 (4224 hom., cov: 32)
• Consequence: VDR ENST00000395324.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 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+29005C>T		intron	N/A	ENSP00000378734.2	P11473-1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20324 AN: 151956 Hom.: 4205 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.0983

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

GnomAD4 genome AF: 0.134 AC: 20386 AN: 152074 Hom.: 4224 Cov.: 32 AF XY: 0.131 AC XY: 9766 AN XY: 74348

African (AFR) AF: 0.443 AC: 18359 AN: 41428

American (AMR) AF: 0.0602 AC: 919 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.0515 AC: 267 AN: 5184

South Asian (SAS) AF: 0.0909 AC: 437 AN: 4810

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10584

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00206 AC: 140 AN: 68008

Other (OTH) AF: 0.0977 AC: 206 AN: 2108

Alfa AF: 0.0931 Hom.: 388

Bravo AF: 0.152

Asia WGS AF: 0.0980 AC: 342 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.049
DANN	Benign	0.68
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7302038;

hg19: chr12-48307641;