chr11-14888688-A-G

Variant names:

• chr11-14888688-A-G
• rs1993116
• NM_024514.5:c.226-2771T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001429699.1(PDE3B):​c.2887-10268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,022 control chromosomes in the GnomAD database, including 32,547 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 0.65 (32547 hom., cov: 32)
• Consequence: PDE3B NM_001429699.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 85 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429699.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	NM_024514.5	MANE Select	c.226-2771T>C		intron	N/A	NP_078790.2
	PDE3B	NM_001429699.1		c.2887-10268A>G		intron	N/A	NP_001416628.1
	PDE3B	NM_001429700.1		c.2887-10257A>G		intron	N/A	NP_001416629.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	ENST00000334636.10	TSL:1 MANE Select	c.226-2771T>C		intron	N/A	ENSP00000334592.5
	CYP2R1	ENST00000530609.5	TSL:1	n.-66+2465T>C		intron	N/A	ENSP00000466060.1
	CYP2R1	ENST00000534686.5	TSL:1	n.-66+2465T>C		intron	N/A	ENSP00000432087.2

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98694 AN: 151904 Hom.: 32489 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.650 AC: 98818 AN: 152022 Hom.: 32547 Cov.: 32 AF XY: 0.654 AC XY: 48610 AN XY: 74322

African (AFR) AF: 0.734 AC: 30409 AN: 41426

American (AMR) AF: 0.673 AC: 10288 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2513 AN: 3472

East Asian (EAS) AF: 0.656 AC: 3394 AN: 5174

South Asian (SAS) AF: 0.663 AC: 3206 AN: 4832

European-Finnish (FIN) AF: 0.574 AC: 6057 AN: 10550

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40801 AN: 67972

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.623 Hom.: 92320

Bravo AF: 0.660

Asia WGS AF: 0.646 AC: 2249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.84
PhyloP100		-0.62
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: rs1993116; hg19: chr11-14910234;