11-14878220-G-T

Position:

• chr11-14878220-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024514.5(CYP2R1):​c.1408C>A​(p.His470Asn) variant causes a missense change. 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: 32)
• Consequence: CYP2R1 NM_024514.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35391307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2R1	NM_024514.5	c.1408C>A	p.His470Asn	missense_variant	5/5	ENST00000334636.10	NP_078790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10	c.1408C>A	p.His470Asn	missense_variant	5/5	1	NM_024514.5	ENSP00000334592.5
CYP2R1	ENST00000532805.1	n.*516C>A		non_coding_transcript_exon_variant	4/4	5		ENSP00000465097.1
CYP2R1	ENST00000532805.1	n.*516C>A		3_prime_UTR_variant	4/4	5		ENSP00000465097.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Vitamin D hydroxylation-deficient rickets, type 1B Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	0.033
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.96	L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.32	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.098	T;D
Sift4G	Benign	0.22	T;T
Polyphen		0.0040	B;B
Vest4		0.44
MutPred		0.39		Loss of helix (P = 0.1706);.;
MVP		0.77
MPC		0.28
ClinPred		0.71	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-14899766;