rs7936142

Variant names:

• chr11-14888199-A-T
• rs7936142
• NM_024514.5:c.226-2282T>A

Variant summary

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

The NM_024514.5(CYP2R1):​c.226-2282T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,144 control chromosomes in the GnomAD database, including 1,011 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 0.10 (1011 hom., cov: 32)
• Consequence: CYP2R1 NM_024514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 9 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 = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024514.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	NM_024514.5	MANE Select	c.226-2282T>A		intron	N/A	NP_078790.2
	PDE3B	NR_190765.1		n.3585A>T		non_coding_transcript_exon	Exon 16 of 16
	PDE3B	NR_190766.1		n.3667A>T		non_coding_transcript_exon	Exon 17 of 17

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	ENST00000334636.10	TSL:1 MANE Select	c.226-2282T>A		intron	N/A	ENSP00000334592.5
	CYP2R1	ENST00000530609.5	TSL:1	n.-65-2282T>A		intron	N/A	ENSP00000466060.1
	CYP2R1	ENST00000534686.5	TSL:1	n.-65-2282T>A		intron	N/A	ENSP00000432087.2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15423 AN: 152026 Hom.: 1011 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.102 AC: 15449 AN: 152144 Hom.: 1011 Cov.: 32 AF XY: 0.0998 AC XY: 7427 AN XY: 74396

African (AFR) AF: 0.182 AC: 7529 AN: 41474

American (AMR) AF: 0.0644 AC: 984 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3470

East Asian (EAS) AF: 0.161 AC: 834 AN: 5176

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4824

European-Finnish (FIN) AF: 0.0452 AC: 479 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0698 AC: 4749 AN: 67994

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.0862 Hom.: 98

Bravo AF: 0.108

Asia WGS AF: 0.132 AC: 459 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7936142; hg19: chr11-14909745;