NM_000785.4:c.*215G>A

Variant names:

• chr12-57762927-C-T
• rs557294448
• NM_000785.4:c.*215G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000785.4(CYP27B1):​c.*215G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP27B1 NM_000785.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000785.4. 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
	CYP27B1	NM_000785.4	MANE Select	c.*215G>A		3_prime_UTR	Exon 9 of 9	NP_000776.1	O15528

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27B1	ENST00000228606.9	TSL:1 MANE Select	c.*215G>A		3_prime_UTR	Exon 9 of 9	ENSP00000228606.4	O15528
	CYP27B1	ENST00000713544.1		c.*215G>A		3_prime_UTR	Exon 9 of 9	ENSP00000518840.1	A0AAA9YHN9
	CYP27B1	ENST00000713545.1		c.*747G>A		3_prime_UTR	Exon 9 of 9	ENSP00000518841.1	A0AAA9YHZ6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 410458 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 218882

African (AFR) AF: 0.00 AC: 0 AN: 12282

American (AMR) AF: 0.00 AC: 0 AN: 24674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13248

East Asian (EAS) AF: 0.00 AC: 0 AN: 25348

South Asian (SAS) AF: 0.00 AC: 0 AN: 49596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 236588

Other (OTH) AF: 0.00 AC: 0 AN: 22946

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-0.58

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

Other links and lift over

dbSNP: rs557294448; hg19: chr12-58156710;