rs7129781

Variant names:

• chr11-14890871-T-C
• rs7129781
• NM_024514.5:c.225+1110A>G

Variant summary

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

The NM_001377215.1(CYP2R1):​c.-281A>G variant causes a 5 prime UTR 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_001377215.1 5_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.338
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377215.1. 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.225+1110A>G		intron	N/A	NP_078790.2
	CYP2R1	NM_001377215.1		c.-281A>G		5_prime_UTR	Exon 1 of 6	NP_001364144.1
	CYP2R1	NM_001400560.1		c.-481A>G		5_prime_UTR	Exon 1 of 7	NP_001387489.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	ENST00000334636.10	TSL:1 MANE Select	c.225+1110A>G		intron	N/A	ENSP00000334592.5	Q6VVX0
	CYP2R1	ENST00000530609.5	TSL:1	n.-66+282A>G		intron	N/A	ENSP00000466060.1	E9PS56
	CYP2R1	ENST00000534686.5	TSL:1	n.-66+282A>G		intron	N/A	ENSP00000432087.2	E9PS56

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

African (AFR) AF: 0.193 AC: 3051 AN: 15782

American (AMR) AF: 0.0508 AC: 50 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 317 AN: 5152

East Asian (EAS) AF: 0.153 AC: 556 AN: 3630

South Asian (SAS) AF: 0.0764 AC: 1258 AN: 16462

European-Finnish (FIN) AF: 0.0580 AC: 16 AN: 276

Middle Eastern (MID) AF: 0.0704 AC: 114 AN: 1620

European-Non Finnish (NFE) AF: 0.0776 AC: 59144 AN: 761880

Other (OTH) AF: 0.0832 AC: 2271 AN: 27300

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

African (AFR) AF: 0.185 AC: 7675 AN: 41462

American (AMR) AF: 0.0651 AC: 995 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 175 AN: 3468

East Asian (EAS) AF: 0.161 AC: 831 AN: 5166

South Asian (SAS) AF: 0.0775 AC: 373 AN: 4816

European-Finnish (FIN) AF: 0.0426 AC: 452 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0699 AC: 4752 AN: 67978

Other (OTH) AF: 0.104 AC: 218 AN: 2106

Alfa AF: 0.0837 Hom.: 2215

Bravo AF: 0.110

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.68
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7129781; hg19: chr11-14912417;