12-47842623-ATTTTTTTTTT-ATTT

Variant names:

• chr12-47842623-ATTTTTTT-A
• rs17878969
• ENST00000550325.5:c.*2116_*2122delAAAAAAA

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 rank	MANE	Protein	UniProt
VDR	NM_000376.3	c.*2116_*2122delAAAAAAA		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.*2116_*2122delAAAAAAA		3_prime_UTR_variant	Exon 10 of 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;