11-59580263-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002556.3(OSBP):c.1789G>A(p.Glu597Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000497 in 1,608,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
OSBP
NM_002556.3 missense
NM_002556.3 missense
Scores
6
5
8
Clinical Significance
Conservation
PhyloP100: 6.07
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OSBP | NM_002556.3 | c.1789G>A | p.Glu597Lys | missense_variant | 11/14 | ENST00000263847.6 | NP_002547.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OSBP | ENST00000263847.6 | c.1789G>A | p.Glu597Lys | missense_variant | 11/14 | 1 | NM_002556.3 | ENSP00000263847.1 | ||
OSBP | ENST00000525357.1 | n.*12G>A | non_coding_transcript_exon_variant | 5/7 | 1 | ENSP00000432399.1 | ||||
OSBP | ENST00000525357.1 | n.*12G>A | 3_prime_UTR_variant | 5/7 | 1 | ENSP00000432399.1 | ||||
ENSG00000255139 | ENST00000661394.1 | n.401+4144C>T | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250790Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135630
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GnomAD4 exome AF: 0.0000494 AC: 72AN: 1456618Hom.: 0 Cov.: 28 AF XY: 0.0000414 AC XY: 30AN XY: 725014
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74348
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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 submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.1789G>A (p.E597K) alteration is located in exon 11 (coding exon 11) of the OSBP gene. This alteration results from a G to A substitution at nucleotide position 1789, causing the glutamic acid (E) at amino acid position 597 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of methylation at E597 (P = 0.0351);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at