Genetic Variant OSBPL5:p.Arg807Gln (chr11-3089927-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020896.4(OSBPL5):c.2420G>A(p.Arg807Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,560,572 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R807L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

OSBPL5
NM_020896.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.503

Publications

1 publications found

Variant links:

Genes affected

OSBPL5 (HGNC:16392): (oxysterol binding protein like 5) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

OSBPL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07759735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSBPL5	NM_020896.4	MANE Select	c.2420G>A	p.Arg807Gln	missense	Exon 21 of 22	NP_065947.1	Q9H0X9-1
OSBPL5	NM_001144063.2		c.2216G>A	p.Arg739Gln	missense	Exon 20 of 21	NP_001137535.1	Q9H0X9-2
OSBPL5	NM_145638.3		c.2216G>A	p.Arg739Gln	missense	Exon 20 of 21	NP_663613.1	Q9H0X9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSBPL5	ENST00000263650.12	TSL:1 MANE Select	c.2420G>A	p.Arg807Gln	missense	Exon 21 of 22	ENSP00000263650.7	Q9H0X9-1
OSBPL5	ENST00000389989.7	TSL:1	c.2216G>A	p.Arg739Gln	missense	Exon 20 of 21	ENSP00000374639.3	Q9H0X9-2
OSBPL5	ENST00000866647.1		c.2420G>A	p.Arg807Gln	missense	Exon 21 of 22	ENSP00000536706.1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000758

AC:

AN:

171514

AF XY:

0.0000651

show subpopulations

Gnomad AFR exome

AF:

0.000297

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000447

AC:

AN:

1408430

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

695592

show subpopulations

African (AFR)

AF:

0.000464

AC:

AN:

32320

American (AMR)

AF:

0.0000530

AC:

AN:

37770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25014

East Asian (EAS)

AF:

0.0000271

AC:

AN:

36954

South Asian (SAS)

AF:

0.000338

AC:

AN:

79916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

1084574

Other (OTH)

AF:

0.0000343

AC:

AN:

58306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41512

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000616

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000459

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000679

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.025

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.83

M_CAP

Benign

0.022

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.50

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

REVEL

Benign

0.024

Sift

Benign

0.11

Sift4G

Benign

0.18

Polyphen

0.58

Vest4

0.16

MVP

0.54

MPC

0.19

ClinPred

0.079

GERP RS

3.2

Varity_R

0.062

gMVP

0.29

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over