dbSNP rs11574010: VDR:c.-83-22345G>A (chr12-47905119-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000395324.6(VDR):c.-83-22345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VDR
ENST00000395324.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.111

Publications

7 publications found

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]

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

VDR links:

ENSG00000278385 (HGNC:):

ENSG00000278385 links:

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new If you want to explore the variant's impact on the transcript ENST00000395324.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VDR	NM_000376.3	MANE Select	c.-248G>A	upstream_gene	N/A	NP_000367.1	P11473-1
VDR	NM_001364085.2		c.-248G>A	upstream_gene	N/A	NP_001351014.1	A0A5K1VW50
VDR	NM_001017536.2		c.-489G>A	upstream_gene	N/A	NP_001017536.1	P11473-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VDR	ENST00000395324.6	TSL:5	c.-83-22345G>A	intron	N/A	ENSP00000378734.2	P11473-1
VDR	ENST00000549336.6	TSL:1 MANE Select	c.-248G>A	upstream_gene	N/A	ENSP00000449573.2	P11473-1
VDR	ENST00000550325.5	TSL:1	c.-489G>A	upstream_gene	N/A	ENSP00000447173.1	P11473-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

5486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

3054

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

110

South Asian (SAS)

AF:

0.00

AC:

AN:

1150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

3228

Other (OTH)

AF:

0.00

AC:

AN:

300

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.9

(source)

DANN

Benign

0.72

PhyloP100

-0.11

PromoterAI

-0.0081

Neutral

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over