dbSNP rs7139166: ENSG00000278385:n.1430C>G (chr12-47906551-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.697

Publications

36 publications found

Variant links:

Genes affected

ENSG00000278385 (HGNC:):

ENSG00000278385 links:

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

VDR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000278385	ENST00000622535.1 link	n.1430C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
VDR	ENST00000395324.6 link	c.-83-23777G>C		intron_variant	Intron 1 of 9	5		ENSP00000378734.2		P11473-1

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46375

AN:

151980

Hom.:

9073

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.357

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.305

AC:

46392

AN:

152100

Hom.:

9075

Cov.:

AF XY:

0.305

AC XY:

22659

AN XY:

74330

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1485

2971

4456

5942

7427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.3

(source)

DANN

Benign

0.62

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over