rs1993116

Positions:

• chr11-14888688-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024514.5(CYP2R1):​c.226-2771T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,022 control chromosomes in the GnomAD database, including 32,547 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 0.65 (32547 hom., cov: 32)
• Consequence: CYP2R1 NM_024514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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]

LOC124902638 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2R1	NM_024514.5	c.226-2771T>C		intron_variant		ENST00000334636.10
LOC124902638	XR_007062603.1	n.866A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2R1	ENST00000334636.10	c.226-2771T>C		intron_variant		1	NM_024514.5	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98694 AN: 151904 Hom.: 32489 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.650 AC: 98818 AN: 152022 Hom.: 32547 Cov.: 32 AF XY: 0.654 AC XY: 48610 AN XY: 74322

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.640

Alfa AF: 0.617 Hom.: 56427

Bravo AF: 0.660

Asia WGS AF: 0.646 AC: 2249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.84

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: rs1993116; hg19: chr11-14910234;