chr11-14882090-T-C

Position:

• chr11-14882090-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2R1	NM_024514.5	c.368-1322A>G		intron_variant		ENST00000334636.10	NP_078790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10	c.368-1322A>G		intron_variant		1	NM_024514.5	ENSP00000334592.5
CYP2R1	ENST00000532805.1	n.78-1322A>G		intron_variant		5		ENSP00000465097.1

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

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.211

Alfa AF: 0.264 Hom.: 7834

Bravo AF: 0.210

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs11023374; hg19: chr11-14903636;