11-14882090-T-C

Variant names:

• chr11-14882090-T-C
• rs11023374
• NM_024514.5:c.368-1322A>G

Variant summary

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

The NM_024514.5(CYP2R1):​c.368-1322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,068 control chromosomes in the GnomAD database, including 4,245 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 0.21 (4245 hom., cov: 32)
• Consequence: CYP2R1 NM_024514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 35 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024514.5. 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
	CYP2R1	NM_024514.5	MANE Select	c.368-1322A>G		intron	N/A	NP_078790.2
	PDE3B	NM_001429699.1		c.2887-16866T>C		intron	N/A	NP_001416628.1
	PDE3B	NM_001429700.1		c.2887-16855T>C		intron	N/A	NP_001416629.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	ENST00000334636.10	TSL:1 MANE Select	c.368-1322A>G		intron	N/A	ENSP00000334592.5	Q6VVX0
	CYP2R1	ENST00000530609.5	TSL:1	n.78-1322A>G		intron	N/A	ENSP00000466060.1	E9PS56
	CYP2R1	ENST00000532805.1	TSL:5	n.78-1322A>G		intron	N/A	ENSP00000465097.1	E9PS56

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31498 AN: 151950 Hom.: 4240 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.207 AC: 31505 AN: 152068 Hom.: 4245 Cov.: 32 AF XY: 0.208 AC XY: 15452 AN XY: 74362

African (AFR) AF: 0.0517 AC: 2146 AN: 41542

American (AMR) AF: 0.348 AC: 5310 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.0906 AC: 468 AN: 5168

South Asian (SAS) AF: 0.221 AC: 1064 AN: 4814

European-Finnish (FIN) AF: 0.197 AC: 2089 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18762 AN: 67920

Other (OTH) AF: 0.211 AC: 446 AN: 2114

Alfa AF: 0.247 Hom.: 11098

Bravo AF: 0.210

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.85
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs11023374; hg19: chr11-14903636;