chr1-51746715-T-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_024586.6(OSBPL9):āc.420T>Gā(p.Phe140Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000427 in 1,608,382 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00022 ( 0 hom., cov: 32)
Exomes š: 0.00045 ( 1 hom. )
Consequence
OSBPL9
NM_024586.6 missense
NM_024586.6 missense
Scores
2
3
13
Clinical Significance
Conservation
PhyloP100: 4.01
Genes affected
OSBPL9 (HGNC:16386): (oxysterol binding protein like 9) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although some members contain only the sterol-binding domain. This family member functions as a cholesterol transfer protein that regulates Golgi structure and function. Multiple transcript variants, most of which encode distinct isoforms, have been identified. Related pseudogenes have been identified on chromosomes 3, 11 and 12. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.27594197).
BS2
High AC in GnomAd4 at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OSBPL9 | NM_024586.6 | c.420T>G | p.Phe140Leu | missense_variant | 6/24 | ENST00000428468.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OSBPL9 | ENST00000428468.6 | c.420T>G | p.Phe140Leu | missense_variant | 6/24 | 1 | NM_024586.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000173 AC: 43AN: 248420Hom.: 1 AF XY: 0.000186 AC XY: 25AN XY: 134274
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GnomAD4 exome AF: 0.000448 AC: 652AN: 1456156Hom.: 1 Cov.: 29 AF XY: 0.000424 AC XY: 307AN XY: 724558
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74370
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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 | Jan 19, 2022 | The c.489T>G (p.F163L) alteration is located in exon 7 (coding exon 7) of the OSBPL9 gene. This alteration results from a T to G substitution at nucleotide position 489, causing the phenylalanine (F) at amino acid position 163 to be replaced by a leucine (L). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.99, 0.99
.;.;D;.;D
Vest4
MVP
MPC
0.11
ClinPred
T
GERP RS
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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