12-47842623-ATTTTTTTTTT-ATTT

Position:

• chr12-47842623-ATTTTTTTTTT-ATTT

Variant summary

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

The ENST00000550325.5(VDR):​c.*2116_*2122delAAAAAAA variant causes a splice region 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 0.00067 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: VDR ENST00000550325.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759

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 nfe. gnomad4 allele frequency = 0.000672 (88/131038) while in subpopulation NFE AF= 0.000723 (46/63640). AF 95% confidence interval is 0.000556. There are 0 homozygotes in gnomad4. There are 46 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VDR	NM_000376.3	c.*2116_*2122delAAAAAAA		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	c.*2116_*2122delAAAAAAA		3_prime_UTR_variant	10/10	1	NM_000376.3	ENSP00000449573.2

Frequencies

GnomAD3 genomes AF: 0.000656 AC: 86 AN: 131038 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000465

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.000234

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.00343

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000723

Gnomad OTH AF: 0.000562

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000672 AC: 88 AN: 131038 Hom.: 0 Cov.: 0 AF XY: 0.000742 AC XY: 46 AN XY: 62024

Gnomad4 AFR AF: 0.000295

Gnomad4 AMR AF: 0.000465

Gnomad4 ASJ AF: 0.000304

Gnomad4 EAS AF: 0.000235

Gnomad4 SAS AF: 0.000247

Gnomad4 FIN AF: 0.00343

Gnomad4 NFE AF: 0.000723

Gnomad4 OTH AF: 0.00112

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;