Variant rs12794714 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024514.5(CYP2R1):c.177C>T(p.Ser59=) 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

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:

LOC124902638 (HGNC:):

LOC124902638 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1165252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-14892029-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CYP2R1	NM_024514.5 linkuse as main transcript	c.177C>T	p.Ser59=	synonymous_variant	1/5	ENST00000334636.10	NP_078790.2
LOC124902638	XR_007062603.1 linkuse as main transcript	n.1484+2723G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10 linkuse as main transcript	c.177C>T	p.Ser59=	synonymous_variant	1/5	1	NM_024514.5	ENSP00000334592	P1

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

GnomAD3 exomes

AF:

0.414

AC:

102443

AN:

247560

Hom.:

22161

AF XY:

0.421

AC XY:

56620

AN XY:

134420

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 SAS exome

AF:

0.455

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

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.355

AC:

54027

AN:

152088

Hom.:

11010

Cov.:

AF XY:

0.360

AC XY:

26792

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.492

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.397

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.429

Hom.:

23606

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Pulmonary disease, chronic obstructive, susceptibility to

Benign:1

protective, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.1

DANN

Benign

0.90

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

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