18-24181183-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_080597.4(OSBPL1A):āc.1774A>Gā(p.Lys592Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 32)
Exomes š: 0.000011 ( 0 hom. )
Consequence
OSBPL1A
NM_080597.4 missense
NM_080597.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
OSBPL1A (HGNC:16398): (oxysterol binding protein like 1A) 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. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms. [provided by RefSeq, Jul 2008]
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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=0.18901703).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OSBPL1A | NM_080597.4 | c.1774A>G | p.Lys592Glu | missense_variant | 19/28 | ENST00000319481.8 | NP_542164.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OSBPL1A | ENST00000319481.8 | c.1774A>G | p.Lys592Glu | missense_variant | 19/28 | 1 | NM_080597.4 | ENSP00000320291.3 | ||
OSBPL1A | ENST00000399443.7 | c.235A>G | p.Lys79Glu | missense_variant | 5/14 | 1 | ENSP00000382372.3 | |||
OSBPL1A | ENST00000357041.8 | c.628A>G | p.Lys210Glu | missense_variant | 7/16 | 2 | ENSP00000349545.4 | |||
OSBPL1A | ENST00000578055.5 | n.139-8700A>G | intron_variant | 5 | ENSP00000462155.1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251232Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135756
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727200
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74342
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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 | Apr 17, 2023 | The c.1774A>G (p.K592E) alteration is located in exon 19 (coding exon 18) of the OSBPL1A gene. This alteration results from a A to G substitution at nucleotide position 1774, causing the lysine (K) at amino acid position 592 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;.;.
Vest4
MVP
MPC
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