rs7129781

chr11-14890871-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.225+1110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 985,164 control chromosomes in the GnomAD database, including 3,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (1041 hom., cov: 31)
  • Exomes 𝑓: 0.080 (2831 hom.)
• Consequence: CYP2R1 NM_024514.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.338

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2R1	NM_024514.5	c.225+1110A>G		intron_variant		ENST00000334636.10
LOC124902638	XR_007062603.1	n.1484+1565T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2R1	ENST00000334636.10	c.225+1110A>G		intron_variant		1	NM_024514.5	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15566 AN: 151960 Hom.: 1041 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0980

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0699

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0802 AC: 66777 AN: 833086 Hom.: 2831 Cov.: 29 AF XY: 0.0797 AC XY: 30647 AN XY: 384712

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.0508

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.0764

Gnomad4 FIN exome AF: 0.0580

Gnomad4 NFE exome AF: 0.0776

Gnomad4 OTH exome AF: 0.0832

GnomAD4 genome AF: 0.103 AC: 15592 AN: 152078 Hom.: 1041 Cov.: 31 AF XY: 0.101 AC XY: 7487 AN XY: 74360

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0651

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.0426

Gnomad4 NFE AF: 0.0699

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0772 Hom.: 570

Bravo AF: 0.110

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.2
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7129781; hg19: chr11-14912417;