dbSNP rs7129781: CYP2R1:c.225+1110A>G (chr11-14890871-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -0.338

Variant links:

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]

CYP2R1 links:

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]

PDE3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CYP2R1	NM_024514.5 link	c.225+1110A>G		intron_variant	Intron 1 of 4	ENST00000334636.10	NP_078790.2	Q6VVX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10 link	c.225+1110A>G		intron_variant	Intron 1 of 4	1	NM_024514.5	ENSP00000334592.5		Q6VVX0

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15566

AN:

151960

Hom.:

1041

Cov.:

show subpopulations

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.:

AF XY:

0.0797

AC XY:

30647

AN XY:

384712

show subpopulations

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.:

AF XY:

0.101

AC XY:

7487

AN XY:

74360

show subpopulations

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

LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over