12-47842623-ATTTTTTTTTT-ATTTTTTTTT

Variant names:

• chr12-47842623-AT-A
• rs17878969
• NM_000376.3:c.*2122delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000376.3(VDR):​c.*2122delA 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 0.031 (116 hom., cov: 0)
  • Failed GnomAD Quality Control
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDR	NM_000376.3	c.*2122delA		3_prime_UTR_variant	Exon 10 of 10	ENST00000549336.6	NP_000367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VDR	ENST00000549336.6	c.*2122delA		3_prime_UTR_variant	Exon 10 of 10	1	NM_000376.3	ENSP00000449573.2
VDR	ENST00000395324.6	c.*2122delA		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000378734.2
VDR	ENST00000550325.5	c.*2122delA		downstream_gene_variant		1		ENSP00000447173.1
VDR	ENST00000229022.9	c.*1921delA		downstream_gene_variant		5		ENSP00000229022.5

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4104 AN: 130958 Hom.: 116 Cov.: 0

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0131

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.00515

Gnomad FIN AF: 0.00180

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.00696

Gnomad OTH AF: 0.0337

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0314 AC: 4111 AN: 130958 Hom.: 116 Cov.: 0 AF XY: 0.0307 AC XY: 1904 AN XY: 62002

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0131

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00180

Gnomad4 NFE AF: 0.00696

Gnomad4 OTH AF: 0.0336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs17878969; hg19: chr12-48236406;