rs12794714

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024514.5(CYP2R1):c.177C>T(p.Ser59Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,612,994 control chromosomes in the GnomAD database, including 142,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11010 hom., cov: 33)

Exomes 𝑓: 0.42 ( 131817 hom. )

Consequence

CYP2R1
NM_024514.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.497

Publications

166 publications found

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 was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 11-14892029-G-A is Benign according to our data. Variant chr11-14892029-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.497 with no splicing effect.

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 rank	MANE	Protein	UniProt
CYP2R1	NM_024514.5 link	c.177C>T	p.Ser59Ser	synonymous_variant	Exon 1 of 5	ENST00000334636.10	NP_078790.2	Q6VVX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10 link	c.177C>T	p.Ser59Ser	synonymous_variant	Exon 1 of 5	1	NM_024514.5	ENSP00000334592.5		Q6VVX0

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

54013

AN:

151968

Hom.:

11008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.363

GnomAD2 exomes

AF:

0.414

AC:

102443

AN:

247560

AF XY:

0.421

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.433

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

AF:

0.421

AC:

615351

AN:

1460906

Hom.:

131817

Cov.:

AF XY:

0.424

AC XY:

308005

AN XY:

726724

show subpopulations

African (AFR)

AF:

0.136

AC:

4536

AN:

33452

American (AMR)

AF:

0.461

AC:

20589

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

13085

AN:

26118

East Asian (EAS)

AF:

0.409

AC:

16233

AN:

39688

South Asian (SAS)

AF:

0.454

AC:

39183

AN:

86226

European-Finnish (FIN)

AF:

0.389

AC:

20699

AN:

53152

Middle Eastern (MID)

AF:

0.450

AC:

2496

AN:

5548

European-Non Finnish (NFE)

AF:

0.426

AC:

474026

AN:

1111696

Other (OTH)

AF:

0.406

AC:

24504

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

22169

44338

66507

88676

110845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14346

28692

43038

57384

71730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.355

AC:

54027

AN:

152088

Hom.:

11010

Cov.:

AF XY:

0.360

AC XY:

26792

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.144

AC:

5987

AN:

41538

American (AMR)

AF:

0.460

AC:

7029

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1707

AN:

3470

East Asian (EAS)

AF:

0.366

AC:

1873

AN:

5124

South Asian (SAS)

AF:

0.454

AC:

2193

AN:

4828

European-Finnish (FIN)

AF:

0.397

AC:

4202

AN:

10582

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29678

AN:

67934

Other (OTH)

AF:

0.366

AC:

772

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1704

3408

5111

6815

8519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.418

Hom.:

37195

Bravo

AF:

0.349

Asia WGS

AF:

0.371

AC:

1291

AN:

3478

EpiCase

AF:

0.458

EpiControl

AF:

0.461

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Pulmonary disease, chronic obstructive, susceptibility to

Benign:1

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:protective

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.1

(source)

DANN

Benign

0.90

PhyloP100

-0.50

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over