rs2238139

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000376.3(VDR):​c.277+2550C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,212 control chromosomes in the GnomAD database, including 48,194 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 0.79 ( 48194 hom., cov: 33)

Consequence

VDR
NM_000376.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VDRNM_000376.3 linkuse as main transcriptc.277+2550C>T intron_variant ENST00000549336.6 NP_000367.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VDRENST00000549336.6 linkuse as main transcriptc.277+2550C>T intron_variant 1 NM_000376.3 ENSP00000449573 P1P11473-1

Frequencies

GnomAD3 genomes
AF:
0.794
AC:
120805
AN:
152094
Hom.:
48155
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.779
Gnomad AMI
AF:
0.743
Gnomad AMR
AF:
0.731
Gnomad ASJ
AF:
0.691
Gnomad EAS
AF:
0.956
Gnomad SAS
AF:
0.836
Gnomad FIN
AF:
0.868
Gnomad MID
AF:
0.747
Gnomad NFE
AF:
0.797
Gnomad OTH
AF:
0.797
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.794
AC:
120902
AN:
152212
Hom.:
48194
Cov.:
33
AF XY:
0.797
AC XY:
59335
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.780
Gnomad4 AMR
AF:
0.731
Gnomad4 ASJ
AF:
0.691
Gnomad4 EAS
AF:
0.957
Gnomad4 SAS
AF:
0.834
Gnomad4 FIN
AF:
0.868
Gnomad4 NFE
AF:
0.797
Gnomad4 OTH
AF:
0.799
Alfa
AF:
0.765
Hom.:
2437
Bravo
AF:
0.783
Asia WGS
AF:
0.902
AC:
3136
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.7
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2238139; hg19: chr12-48256280; API