12-47842623-ATTTTTTTTTT-ATTTTTTTTTTTTTTTTTT

Position:

• chr12-47842623-ATTTTTTTTTT-ATTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000376.3(VDR):​c.*2122_*2123insAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00034 (0 hom., cov: 0)
• Consequence: VDR NM_000376.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VDR	NM_000376.3	c.*2122_*2123insAAAAAAAA		3_prime_UTR_variant	10/10	ENST00000549336.6	NP_000367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VDR	ENST00000549336.6	c.*2122_*2123insAAAAAAAA		3_prime_UTR_variant	10/10	1	NM_000376.3	ENSP00000449573	P1
VDR	ENST00000395324.6	c.*2122_*2123insAAAAAAAA		3_prime_UTR_variant	10/10	5		ENSP00000378734	P1
VDR	ENST00000550325.5			downstream_gene_variant		1		ENSP00000447173
VDR	ENST00000229022.9			downstream_gene_variant		5		ENSP00000229022

Frequencies

GnomAD3 genomes AF: 0.000343 AC: 45 AN: 131050 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000237

Gnomad AMI AF: 0.00117

Gnomad AMR AF: 0.000155

Gnomad ASJ AF: 0.000608

Gnomad EAS AF: 0.000468

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.000327

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000424

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000343 AC: 45 AN: 131050 Hom.: 0 Cov.: 0 AF XY: 0.000290 AC XY: 18 AN XY: 62012

Gnomad4 AFR AF: 0.000237

Gnomad4 AMR AF: 0.000155

Gnomad4 ASJ AF: 0.000608

Gnomad4 EAS AF: 0.000468

Gnomad4 SAS AF: 0.000245

Gnomad4 FIN AF: 0.000327

Gnomad4 NFE AF: 0.000424

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17878969; hg19: chr12-48236406;