11-14888727-T-G

Variant names:

• chr11-14888727-T-G
• rs10500804
• NM_024514.5:c.226-2810A>C

Variant summary

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

The NM_024514.5(CYP2R1):​c.226-2810A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,116 control chromosomes in the GnomAD database, including 11,032 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 0.36 (11032 hom., cov: 32)
• Consequence: CYP2R1 NM_024514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 53 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 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.226-2810A>C		intron	N/A	NP_078790.2
	PDE3B	NM_001429699.1		c.2887-10229T>G		intron	N/A	NP_001416628.1
	PDE3B	NM_001429700.1		c.2887-10218T>G		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.226-2810A>C		intron	N/A	ENSP00000334592.5	Q6VVX0
	CYP2R1	ENST00000530609.5	TSL:1	n.-66+2426A>C		intron	N/A	ENSP00000466060.1	E9PS56
	CYP2R1	ENST00000534686.5	TSL:1	n.-66+2426A>C		intron	N/A	ENSP00000432087.2	E9PS56

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54077 AN: 151998 Hom.: 11030 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.356 AC: 54091 AN: 152116 Hom.: 11032 Cov.: 32 AF XY: 0.361 AC XY: 26834 AN XY: 74384

African (AFR) AF: 0.144 AC: 5976 AN: 41508

American (AMR) AF: 0.460 AC: 7025 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1732 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1906 AN: 5178

South Asian (SAS) AF: 0.456 AC: 2197 AN: 4822

European-Finnish (FIN) AF: 0.395 AC: 4177 AN: 10584

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29718 AN: 67968

Other (OTH) AF: 0.367 AC: 774 AN: 2110

Alfa AF: 0.426 Hom.: 20082

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		-0.0020
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: rs10500804; hg19: chr11-14910273;