Variant chr12-57763498-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000228606.9(CYP27B1):c.1413+113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,023,504 control chromosomes in the GnomAD database, including 844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.048 ( 231 hom., cov: 32)

Exomes 𝑓: 0.035 ( 613 hom. )

Consequence

CYP27B1
ENST00000228606.9 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-57763498-T-G is Benign according to our data. Variant chr12-57763498-T-G is described in ClinVar as [Benign]. Clinvar id is 1266201.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0822 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.1413+113A>C		intron_variant		ENST00000228606.9	NP_000776.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
CYP27B1	ENST00000228606.9 linkuse as main transcript	c.1413+113A>C	intron_variant	1	NM_000785.4	ENSP00000228606	P1
CYP27B1	ENST00000713544.1 linkuse as main transcript	c.1494+113A>C	intron_variant			ENSP00000518840
CYP27B1	ENST00000713545.1 linkuse as main transcript	c.*418+113A>C	intron_variant			ENSP00000518841
CYP27B1	ENST00000547344.5 linkuse as main transcript	n.1552+113A>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

7342

AN:

152128

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0848

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.0298

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0365

Gnomad OTH

AF:

0.0402

GnomAD4 exome

AF:

0.0352

AC:

30704

AN:

871258

Hom.:

613

AF XY:

0.0345

AC XY:

15786

AN XY:

457874

show subpopulations

Gnomad4 AFR exome

AF:

0.0916

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0252

Gnomad4 EAS exome

AF:

0.0291

Gnomad4 SAS exome

AF:

0.0284

Gnomad4 FIN exome

AF:

0.0340

Gnomad4 NFE exome

AF:

0.0354

Gnomad4 OTH exome

AF:

0.0349

GnomAD4 genome

AF:

0.0482

AC:

7339

AN:

152246

Hom.:

231

Cov.:

AF XY:

0.0466

AC XY:

3470

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0846

Gnomad4 AMR

AF:

0.0350

Gnomad4 ASJ

AF:

0.0279

Gnomad4 EAS

AF:

0.0300

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0366

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.0410

Hom.:

Bravo

AF:

0.0507

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.50

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over