12-47842623-ATTTTTTTTTT-ATTTTTTTTTTTTTTTTTT

Variant names:

• chr12-47842623-A-ATTTTTTTT
• rs17878969
• NM_000376.3:c.*2115_*2122dupAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_000376.3(VDR):​c.*2115_*2122dupAAAAAAAA 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000343 (45/131050) while in subpopulation EAS AF= 0.000468 (2/4270). AF 95% confidence interval is 0.000298. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDR	NM_000376.3	c.*2115_*2122dupAAAAAAAA		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.*2115_*2122dupAAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_000376.3	ENSP00000449573.2
VDR	ENST00000395324.6	c.*2115_*2122dupAAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000378734.2
VDR	ENST00000550325.5	c.*2115_*2122dupAAAAAAAA		downstream_gene_variant		1		ENSP00000447173.1
VDR	ENST00000229022.9	c.*1914_*1921dupAAAAAAAA		downstream_gene_variant		5		ENSP00000229022.5

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;