12-57768115-G-C

Variant names:

• chr12-57768115-G-C
• rs3782130
• ENST00000546609.2:n.107+765C>G

Variant summary

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

The ENST00000546609.2(CYP27B1):​n.107+765C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,036 control chromosomes in the GnomAD database, including 6,986 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 0.28 (6986 hom., cov: 32)
• Consequence: CYP27B1 ENST00000546609.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 41 publications found

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 Gene-Disease associations (from GenCC):

• vitamin D-dependent rickets, type 1A

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• vitamin D-dependent rickets, type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 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
CYP27B1	ENST00000546609.2	n.107+765C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42618 AN: 151918 Hom.: 6979 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.280 AC: 42644 AN: 152036 Hom.: 6986 Cov.: 32 AF XY: 0.288 AC XY: 21419 AN XY: 74298

African (AFR) AF: 0.133 AC: 5529 AN: 41496

American (AMR) AF: 0.263 AC: 4017 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3343 AN: 5142

South Asian (SAS) AF: 0.489 AC: 2357 AN: 4816

European-Finnish (FIN) AF: 0.377 AC: 3975 AN: 10554

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21512 AN: 67948

Other (OTH) AF: 0.250 AC: 530 AN: 2116

Alfa AF: 0.183 Hom.: 400

Bravo AF: 0.265

Asia WGS AF: 0.523 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		0.015

Splicing

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

Other links and lift over

dbSNP: rs3782130; hg19: chr12-58161898;