dbSNP rs143116125: OSBPL2:p.Arg43Lys (chr20-62260071-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144498.4(OSBPL2):c.128G>A(p.Arg43Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

OSBPL2
NM_144498.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

OSBPL2 (HGNC:15761): (oxysterol binding protein like 2) 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 the encoded protein contains only the sterol-binding domain. In vitro studies have shown that the encoded protein can bind strongly to phosphatic acid and weakly to phosphatidylinositol 3-phosphate, but cannot bind to 25-hydroxycholesterol. The protein associates with the Golgi apparatus. Transcript variants encoding different isoforms have been described. [provided by RefSeq, Sep 2014]

OSBPL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10182974).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL2	NM_144498.4 link	c.128G>A	p.Arg43Lys	missense_variant	Exon 3 of 14	ENST00000313733.9	NP_653081.1	Q9H1P3-1
OSBPL2	NM_014835.5 link	c.92G>A	p.Arg31Lys	missense_variant	Exon 3 of 14		NP_055650.1	Q9H1P3-2
OSBPL2	NM_001363878.2 link	c.-239G>A		5_prime_UTR_variant	Exon 3 of 15		NP_001350807.1
OSBPL2	NM_001278649.3 link	c.-184-3545G>A		intron_variant	Intron 2 of 12		NP_001265578.1	E7ET92B4DKJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9 link	c.128G>A	p.Arg43Lys	missense_variant	Exon 3 of 14	1	NM_144498.4	ENSP00000316649.3		Q9H1P3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251448

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000165

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.020

.;T;.;.;T;.;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.66

T;.;T;T;.;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.;.;L;.;.;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.37

.;N;.;N;.;.;.;.

REVEL

Benign

0.069

Sift

Benign

0.68

.;T;.;T;.;.;.;.

Sift4G

Benign

0.94

T;T;.;T;.;.;.;.

Polyphen

0.028, 0.057

.;B;.;B;B;.;.;B

Vest4

0.12, 0.14

MutPred

0.35

Gain of ubiquitination at R43 (P = 0.0162);Gain of ubiquitination at R43 (P = 0.0162);Gain of ubiquitination at R43 (P = 0.0162);.;Gain of ubiquitination at R43 (P = 0.0162);.;Gain of ubiquitination at R43 (P = 0.0162);Gain of ubiquitination at R43 (P = 0.0162);

MVP

0.23

MPC

0.63

ClinPred

0.17

GERP RS

4.7

Varity_R

0.073

gMVP

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over