12-47842623-ATTTTTTTTTT-ATTTT

Variant names:

• chr12-47842623-ATTTTTT-A
• rs17878969
• ENST00000550325.5:c.*2117_*2122delAAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000550325.5(VDR):​c.*2117_*2122delAAAAAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (7283 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: VDR ENST00000550325.5 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 12-47842623-ATTTTTT-A is Benign according to our data. Variant chr12-47842623-ATTTTTT-A is described in ClinVar as [Benign]. Clinvar id is 308832.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDR	NM_000376.3	c.*2117_*2122delAAAAAA		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.*2117_*2122delAAAAAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_000376.3	ENSP00000449573.2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 44435 AN: 131096 Hom.: 7284 Cov.: 0

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.339 AC: 44437 AN: 131098 Hom.: 7283 Cov.: 0 AF XY: 0.338 AC XY: 20999 AN XY: 62068

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.0668

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.341

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Vitamin D-dependent rickets Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;