rs7139166

Variant names:

• chr12-47906551-C-G
• rs7139166
• ENST00000395324.6:c.-83-23777G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000622535.1(ENSG00000278385):​n.1430C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,120 control chromosomes in the GnomAD database, including 9,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (9075 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: ENSG00000278385 ENST00000622535.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• Publications: 36 publications found

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]

VDR Gene-Disease associations (from GenCC):

• vitamin D-dependent rickets, type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• vitamin D-dependent rickets, type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000278385 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622535.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDR	ENST00000395324.6	TSL:5	c.-83-23777G>C		intron	N/A	ENSP00000378734.2	P11473-1
	ENSG00000278385	ENST00000622535.1	TSL:6	n.1430C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46375 AN: 151980 Hom.: 9073 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.300 AC: 6 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.357 AC XY: 5 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.286 AC: 4 AN: 14

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.305 AC: 46392 AN: 152100 Hom.: 9075 Cov.: 32 AF XY: 0.305 AC XY: 22659 AN XY: 74330

African (AFR) AF: 0.0856 AC: 3555 AN: 41514

American (AMR) AF: 0.309 AC: 4719 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5182

South Asian (SAS) AF: 0.228 AC: 1102 AN: 4826

European-Finnish (FIN) AF: 0.475 AC: 5011 AN: 10556

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29573 AN: 67954

Other (OTH) AF: 0.314 AC: 663 AN: 2110

Alfa AF: 0.367 Hom.: 1433

Bravo AF: 0.282

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.62
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7139166; hg19: chr12-48300334;