11-14888727-T-G

Position:

• chr11-14888727-T-G

Variant summary

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

The NM_024514.5(CYP2R1):​c.226-2810A>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

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 (AMR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2R1	NM_024514.5	c.226-2810A>C		intron_variant		ENST00000334636.10	NP_078790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10	c.226-2810A>C		intron_variant		1	NM_024514.5	ENSP00000334592.5

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.367

Alfa AF: 0.437 Hom.: 15642

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.80

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: rs10500804; hg19: chr11-14910273;