chr12-47908762-C-T

Variant summary

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

The ENST00000395324.6(VDR):​c.-83-25988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,090 control chromosomes in the GnomAD database, including 16,359 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 ( 16359 hom., cov: 31)

Consequence

VDR
ENST00000395324.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.203
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VDRENST00000395324.6 linkc.-83-25988G>A intron_variant Intron 1 of 9 5 ENSP00000378734.2 P11473-1

Frequencies

GnomAD3 genomes
AF:
0.378
AC:
57431
AN:
151972
Hom.:
16322
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.800
Gnomad AMI
AF:
0.172
Gnomad AMR
AF:
0.233
Gnomad ASJ
AF:
0.247
Gnomad EAS
AF:
0.423
Gnomad SAS
AF:
0.323
Gnomad FIN
AF:
0.155
Gnomad MID
AF:
0.282
Gnomad NFE
AF:
0.199
Gnomad OTH
AF:
0.354
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.378
AC:
57511
AN:
152090
Hom.:
16359
Cov.:
31
AF XY:
0.373
AC XY:
27764
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.801
Gnomad4 AMR
AF:
0.233
Gnomad4 ASJ
AF:
0.247
Gnomad4 EAS
AF:
0.422
Gnomad4 SAS
AF:
0.322
Gnomad4 FIN
AF:
0.155
Gnomad4 NFE
AF:
0.199
Gnomad4 OTH
AF:
0.351
Alfa
AF:
0.281
Hom.:
3191
Bravo
AF:
0.403
Asia WGS
AF:
0.386
AC:
1341
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.92
DANN
Benign
0.17

Splicing

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: rs11568820; hg19: chr12-48302545; API