NM_000785.4(CYP27B1):c.320G>A (p.Arg107His) AND Vitamin D-dependent rickets, type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 27, 2017
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000001725.7

Allele description [Variation Report for NM_000785.4(CYP27B1):c.320G>A (p.Arg107His)]

NM_000785.4(CYP27B1):c.320G>A (p.Arg107His)

Gene:

CYP27B1:cytochrome P450 family 27 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q14.1

Genomic location:

Preferred name:

NM_000785.4(CYP27B1):c.320G>A (p.Arg107His)

HGVS:

NC_000012.12:g.57766073C>T
NG_007076.1:g.6121G>A
NM_000785.4:c.320G>AMANE SELECT
NP_000776.1:p.Arg107His
NC_000012.11:g.58159856C>T
NM_000785.3:c.320G>A
O15528:p.Arg107His

Protein change:

R107H; ARG107HIS

Links:

UniProtKB: O15528#VAR_016952; OMIM: 609506.0001; dbSNP: rs28934604

NCBI 1000 Genomes Browser:

rs28934604

Molecular consequence:

NM_000785.4:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Vitamin D-dependent rickets, type 1 (VDD1)
Synonyms:: VITAMIN D DEPENDENCY, TYPE 1
Identifiers:: MONDO: MONDO:0009924; MedGen: C0268689; Orphanet: 289157

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000380514	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Likely pathogenic (Apr 27, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9486994, 23423976, 10518789, 11737215, 25284246 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000380514

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Likely pathogenic
(Apr 27, 2017)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets.

Kitanaka S, Takeyama K, Murayama A, Sato T, Okumura K, Nogami M, Hasegawa Y, Niimi H, Yanagisawa J, Tanaka T, Kato S.

N Engl J Med. 1998 Mar 5;338(10):653-61.

PubMed [citation]

PMID:: 9486994

CYP24A1 and CYP27B1 polymorphisms modulate vitamin D metabolism in colon cancer cells.

Jacobs ET, Van Pelt C, Forster RE, Zaidi W, Hibler EA, Galligan MA, Haussler MR, Jurutka PW.

Cancer Res. 2013 Apr 15;73(8):2563-73. doi: 10.1158/0008-5472.CAN-12-4134. Epub 2013 Feb 19.

PubMed [citation]

PMID:: 23423976
PMCID:: PMC3630267

See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000380514.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The CYP27B1 c.320G>A (p.Arg107His) missense variant is reported in two studies in which it is found in three patients with vitamin D-dependent rickets, including in one patient who carried the variant in a homozygous state and in two brothers who were compound heterozygous for the p.Arg107His variant and a null variant (Kitanaka et al. 1998; Miyai et al. 2015). Control data are unavailable for this variant, which is not reported in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium or the Genome Aggregation Database. The p.Arg107His variant was found to result in significantly reduced protein expression and no detectable protein activity as compared to wild type (Sawada et al. 1999; Sawada et al. 2001; Jacobs et al. 2013). Based on the evidence, the p.Arg107His variant is classified as likely pathogenic for vitamin D-dependent rickets. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 9, 2023

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