rs7935792

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.383
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CYP2R1NM_024514.5 linkc.226-1998T>G intron_variant ENST00000334636.10 NP_078790.2 Q6VVX0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP2R1ENST00000334636.10 linkc.226-1998T>G intron_variant 1 NM_024514.5 ENSP00000334592.5 Q6VVX0

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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