Genetic Variant OSBPL5:p.Ala774Thr (chr11-3090636-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020896.4(OSBPL5):c.2320G>A(p.Ala774Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,612,596 control chromosomes in the GnomAD database, including 34,431 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3158 hom., cov: 34)

Exomes 𝑓: 0.20 ( 31273 hom. )

Consequence

OSBPL5
NM_020896.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

Publications

25 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033494234).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL5	NM_020896.4 link	c.2320G>A	p.Ala774Thr	missense_variant	Exon 20 of 22	ENST00000263650.12	NP_065947.1	Q9H0X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL5	ENST00000263650.12 link	c.2320G>A	p.Ala774Thr	missense_variant	Exon 20 of 22	1	NM_020896.4	ENSP00000263650.7		Q9H0X9-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29252

AN:

152152

Hom.:

3157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.0343

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.161

GnomAD2 exomes

AF:

0.194

AC:

48302

AN:

248928

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0902

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.200

AC:

291829

AN:

1460324

Hom.:

31273

Cov.:

AF XY:

0.203

AC XY:

147227

AN XY:

726460

show subpopulations

African (AFR)

AF:

0.157

AC:

5239

AN:

33474

American (AMR)

AF:

0.0951

AC:

4248

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4781

AN:

26108

East Asian (EAS)

AF:

0.0611

AC:

2425

AN:

39686

South Asian (SAS)

AF:

0.278

AC:

23950

AN:

86228

European-Finnish (FIN)

AF:

0.358

AC:

18701

AN:

52284

Middle Eastern (MID)

AF:

0.176

AC:

1015

AN:

5762

European-Non Finnish (NFE)

AF:

0.198

AC:

220090

AN:

1111748

Other (OTH)

AF:

0.189

AC:

11380

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

12777

25553

38330

51106

63883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7510

15020

22530

30040

37550

<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:

0.192

AC:

29267

AN:

152272

Hom.:

3158

Cov.:

AF XY:

0.199

AC XY:

14817

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.160

AC:

6651

AN:

41572

American (AMR)

AF:

0.140

AC:

2141

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

673

AN:

3472

East Asian (EAS)

AF:

0.0344

AC:

178

AN:

5174

South Asian (SAS)

AF:

0.267

AC:

1288

AN:

4832

European-Finnish (FIN)

AF:

0.372

AC:

3947

AN:

10598

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13776

AN:

68004

Other (OTH)

AF:

0.163

AC:

344

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1195

2390

3585

4780

5975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.189

Hom.:

1821

Bravo

AF:

0.166

TwinsUK

AF:

0.199

AC:

739

ALSPAC

AF:

0.196

AC:

756

ESP6500AA

AF:

0.155

AC:

683

ESP6500EA

AF:

0.194

AC:

1668

ExAC

AF:

0.198

AC:

23970

Asia WGS

AF:

0.159

AC:

550

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0033

.;T;.;T;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.54

T;T;.;T;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

.;N;.;.;.;.

PhyloP100

2.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.080

N;N;N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.59

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

.;B;.;.;.;.

Vest4

0.026

MPC

0.14

ClinPred

0.0098

GERP RS

2.7

Varity_R

0.055

gMVP

0.19

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over