rs782488944

Variant names:

• chr11-14878128-T-C
• rs782488944
• NM_024514.5:c.1500A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-14878128-T-C
• chr11-14878128-T-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024514.5(CYP2R1):​c.1500A>G​(p.Arg500Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP2R1 NM_024514.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-14878128-T-C is Benign according to our data. Variant chr11-14878128-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2693212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.21 with no splicing effect.

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.1500A>G	p.Arg500Arg	synonymous	Exon 5 of 5	NP_078790.2
	CYP2R1	NM_001400568.1		c.1455A>G	p.Arg485Arg	synonymous	Exon 5 of 5	NP_001387497.1
	CYP2R1	NM_001400567.1		c.1356A>G	p.Arg452Arg	synonymous	Exon 6 of 6	NP_001387496.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2R1	ENST00000334636.10	TSL:1 MANE Select	c.1500A>G	p.Arg500Arg	synonymous	Exon 5 of 5	ENSP00000334592.5	Q6VVX0
	CYP2R1	ENST00000530609.5	TSL:1	n.*1096A>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000466060.1	E9PS56
	CYP2R1	ENST00000532805.1	TSL:5	n.*608A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000465097.1	E9PS56

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.4
DANN	Benign	0.65
PhyloP100		2.2

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: rs782488944; hg19: chr11-14899674;