rs7935792

Positions:

• chr11-14887915-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024514.5(CYP2R1):​c.226-1998T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,184 control chromosomes in the GnomAD database, including 1,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1021 hom., cov: 32)
• Consequence: CYP2R1 NM_024514.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2R1	NM_024514.5	c.226-1998T>G		intron_variant		ENST00000334636.10	NP_078790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2R1	ENST00000334636.10	c.226-1998T>G		intron_variant		1	NM_024514.5	ENSP00000334592.5

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15445 AN: 152066 Hom.: 1021 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15470 AN: 152184 Hom.: 1021 Cov.: 32 AF XY: 0.0999 AC XY: 7437 AN XY: 74408

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0647

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0700

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0769 Hom.: 719

Bravo AF: 0.108

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.36

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: rs7935792; hg19: chr11-14909461; COSMIC: COSV58127333; COSMIC: COSV58127333;