Variant 11-14878193-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024514.5(CYP2R1):c.1435C>G(p.Pro479Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,054 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CYP2R1
NM_024514.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.77

Variant links:

Genes affected

CYP2R1 (HGNC:20580): (cytochrome P450 family 2 subfamily R 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. This enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into the active ligand for the vitamin D receptor. A mutation in this gene has been associated with selective 25-hydroxyvitamin D deficiency. [provided by RefSeq, Jul 2008]

CYP2R1 links:

PDE3B (HGNC:8779): (phosphodiesterase 3B) Enables 3',5'-cyclic-nucleotide phosphodiesterase activity. Involved in negative regulation of angiogenesis; negative regulation of cell adhesion; and negative regulation of lipid catabolic process. Located in membrane. Part of guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

PDE3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2R1	NM_024514.5 linkuse as main transcript	c.1435C>G	p.Pro479Ala	missense_variant	5/5	ENST00000334636.10	NP_078790.2	Q6VVX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYP2R1	ENST00000334636.10 linkuse as main transcript	c.1435C>G	p.Pro479Ala	missense_variant	5/5	1	NM_024514.5	ENSP00000334592.5	Q6VVX0
CYP2R1	ENST00000532805.1 linkuse as main transcript	n.*543C>G		non_coding_transcript_exon_variant	4/4	5		ENSP00000465097.1	E9PS56
CYP2R1	ENST00000532805.1 linkuse as main transcript	n.*543C>G		3_prime_UTR_variant	4/4	5		ENSP00000465097.1	E9PS56

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250742

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461054

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vitamin D hydroxylation-deficient rickets, type 1B

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.38

Sift

Benign

0.76

T;T

Sift4G

Benign

0.16

T;T

Polyphen

1.0

D;P

Vest4

0.51

MutPred

0.69

Loss of disorder (P = 0.0741);.;

MVP

0.83

MPC

0.45

ClinPred

0.94

GERP RS

4.8

Varity_R

0.51

gMVP

0.77

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