11-59580251-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002556.3(OSBP):​c.1801G>T​(p.Val601Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OSBP
NM_002556.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.424
Variant links:
Genes affected
OSBP (HGNC:8503): (oxysterol binding protein) Oxysterol binding protein is an intracellular protein that is believed to transport sterols from lysosomes to the nucleus where the sterol down-regulates the genes for the LDL receptor, HMG-CoA reductase, and HMG synthetase [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22483751).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSBPNM_002556.3 linkuse as main transcriptc.1801G>T p.Val601Leu missense_variant 11/14 ENST00000263847.6 NP_002547.1 P22059

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSBPENST00000263847.6 linkuse as main transcriptc.1801G>T p.Val601Leu missense_variant 11/141 NM_002556.3 ENSP00000263847.1 P22059
OSBPENST00000525357.1 linkuse as main transcriptn.*24G>T non_coding_transcript_exon_variant 5/71 ENSP00000432399.1 H0YCV6
OSBPENST00000525357.1 linkuse as main transcriptn.*24G>T 3_prime_UTR_variant 5/71 ENSP00000432399.1 H0YCV6
ENSG00000255139ENST00000661394.1 linkuse as main transcriptn.401+4132C>A intron_variant

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250992
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135706
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459844
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
726402
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 27, 2023The c.1801G>T (p.V601L) alteration is located in exon 11 (coding exon 11) of the OSBP gene. This alteration results from a G to T substitution at nucleotide position 1801, causing the valine (V) at amino acid position 601 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.61
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.069
Sift
Benign
0.15
T
Sift4G
Benign
0.20
T
Polyphen
0.023
B
Vest4
0.21
MutPred
0.47
Loss of methylation at K604 (P = 0.0885);
MVP
0.14
MPC
0.92
ClinPred
0.26
T
GERP RS
3.5
Varity_R
0.13
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1210953565; hg19: chr11-59347724; API