chr11-14892029-G-A

Variant names:

• chr11-14892029-G-A
• rs12794714
• NM_024514.5:c.177C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.497
• Publications: 166 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	NM_024514.5	MANE Select	c.177C>T	p.Ser59Ser	synonymous	Exon 1 of 5	NP_078790.2
	PDE3B	NM_001429699.1		c.2887-6927G>A		intron	N/A	NP_001416628.1
	PDE3B	NM_001429700.1		c.2887-6916G>A		intron	N/A	NP_001416629.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	ENST00000334636.10	TSL:1 MANE Select	c.177C>T	p.Ser59Ser	synonymous	Exon 1 of 5	ENSP00000334592.5	Q6VVX0
	CYP2R1	ENST00000921520.1		c.177C>T	p.Ser59Ser	synonymous	Exon 1 of 5	ENSP00000591579.1
	CYP2R1	ENST00000921519.1		c.177C>T	p.Ser59Ser	synonymous	Exon 1 of 4	ENSP00000591578.1

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

GnomAD2 exomes AF: 0.414 AC: 102443 AN: 247560 AF XY: 0.421

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

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

GnomAD4 genome AF: 0.355 AC: 54027 AN: 152088 Hom.: 11010 Cov.: 33 AF XY: 0.360 AC XY: 26792 AN XY: 74344

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.1
DANN	Benign	0.90
PhyloP100		-0.50
PromoterAI		-0.11	Neutral
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: rs12794714; hg19: chr11-14913575; COSMIC: COSV58128076; COSMIC: COSV58128076;