rs12794714

chr11-14892029-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.497

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]

LOC124902638 (HGNC:):

ACMG classification

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	UniProt
CYP2R1	NM_024514.5	c.177C>T	p.Ser59=	synonymous_variant	1/5	ENST00000334636.10
LOC124902638	XR_007062603.1	n.1484+2723G>A		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.355 AC: 54013 AN: 151968 Hom.: 11008 Cov.: 33

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

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.: 66 AF XY: 0.424 AC XY: 308005 AN XY: 726724

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.: 33 AF XY: 0.360 AC XY: 26792 AN XY: 74344

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

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

Other links and lift over

dbSNP: rs12794714; hg19: chr11-14913575; COSMIC: COSV58128076; COSMIC: COSV58128076;