Variant 12-57764205-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000785.4(CYP27B1):c.1137-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,594,334 control chromosomes in the GnomAD database, including 102,530 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 0.32 ( 8528 hom., cov: 33)

Exomes 𝑓: 0.35 ( 94002 hom. )

Consequence

CYP27B1
NM_000785.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.183

Variant links:

Genes affected

CYP27B1 (HGNC:2606): (cytochrome P450 family 27 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the inner mitochondrial membrane where it hydroxylates 25-hydroxyvitamin D3 at the 1alpha position. This reaction synthesizes 1alpha,25-dihydroxyvitamin D3, the active form of vitamin D3, which binds to the vitamin D receptor and regulates calcium metabolism. Thus this enzyme regulates the level of biologically active vitamin D and plays an important role in calcium homeostasis. Mutations in this gene can result in vitamin D-dependent rickets type I. [provided by RefSeq, Jul 2008]

CYP27B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP27B1	NM_000785.4 linkuse as main transcript	c.1137-29T>C		intron_variant		ENST00000228606.9	NP_000776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP27B1	ENST00000228606.9 linkuse as main transcript	c.1137-29T>C		intron_variant		1	NM_000785.4	ENSP00000228606	P1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49195

AN:

152066

Hom.:

8503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.378

AC:

95027

AN:

251222

Hom.:

19719

AF XY:

0.385

AC XY:

52324

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.635

Gnomad SAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.350

AC:

504508

AN:

1442148

Hom.:

94002

Cov.:

AF XY:

0.355

AC XY:

255381

AN XY:

718886

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.544

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.324

AC:

49269

AN:

152186

Hom.:

8528

Cov.:

AF XY:

0.331

AC XY:

24669

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.286

Gnomad4 EAS

AF:

0.655

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.327

Hom.:

4688

Bravo

AF:

0.311

Asia WGS

AF:

0.599

AC:

2079

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over