18-24181183-T-C

Variant summary

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

The NM_080597.4(OSBPL1A):ā€‹c.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

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63
Variant links:
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]

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=0.18901703).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSBPL1ANM_080597.4 linkuse as main transcriptc.1774A>G p.Lys592Glu missense_variant 19/28 ENST00000319481.8 NP_542164.2 Q9BXW6-1B0YJ56B3KU11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSBPL1AENST00000319481.8 linkuse as main transcriptc.1774A>G p.Lys592Glu missense_variant 19/281 NM_080597.4 ENSP00000320291.3 Q9BXW6-1
OSBPL1AENST00000399443.7 linkuse as main transcriptc.235A>G p.Lys79Glu missense_variant 5/141 ENSP00000382372.3 Q9BXW6-2
OSBPL1AENST00000357041.8 linkuse as main transcriptc.628A>G p.Lys210Glu missense_variant 7/162 ENSP00000349545.4 Q9BXW6-4
OSBPL1AENST00000578055.5 linkuse as main transcriptn.139-8700A>G intron_variant 5 ENSP00000462155.1 J3KRT6

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000579
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251232
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.000492
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461824
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000579
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000322
Hom.:
0
Bravo
AF:
0.000162
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

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 GeneticsApr 17, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.035
T;.;.
Eigen
Benign
-0.0048
Eigen_PC
Benign
0.093
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;.;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.089
Sift
Benign
0.083
T;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.45
P;.;.
Vest4
0.47
MVP
0.35
MPC
0.99
ClinPred
0.13
T
GERP RS
3.4
Varity_R
0.56
gMVP
0.64

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: rs146249824; hg19: chr18-21761147; API