20-62260019-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144498.4(OSBPL2):c.76G>A(p.Ala26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,896 control chromosomes in the GnomAD database, including 73 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 Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 35 hom. )

Consequence

OSBPL2
NM_144498.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.508

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021491945).

BP6

Variant 20-62260019-G-A is Benign according to our data. Variant chr20-62260019-G-A is described in ClinVar as [Benign]. Clinvar id is 667053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1626/152248) while in subpopulation AFR AF = 0.0375 (1558/41542). AF 95% confidence interval is 0.036. There are 38 homozygotes in GnomAd4. There are 776 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 1626 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL2	NM_144498.4 link	c.76G>A	p.Ala26Thr	missense_variant	Exon 3 of 14	ENST00000313733.9	NP_653081.1	Q9H1P3-1
OSBPL2	NM_014835.5 link	c.40G>A	p.Ala14Thr	missense_variant, splice_region_variant	Exon 3 of 14		NP_055650.1	Q9H1P3-2
OSBPL2	NM_001363878.2 link	c.-291G>A		5_prime_UTR_variant	Exon 3 of 15		NP_001350807.1
OSBPL2	NM_001278649.3 link	c.-184-3597G>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.76G>A	p.Ala26Thr	missense_variant	Exon 3 of 14	1	NM_144498.4	ENSP00000316649.3		Q9H1P3-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1619

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00268

AC:

675

AN:

251410

AF XY:

0.00204

show subpopulations

Gnomad AFR exome

AF:

0.0372

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00110

AC:

1602

AN:

1461648

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

704

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0382

AC:

1280

AN:

33470

Gnomad4 AMR exome

AF:

0.00195

AC:

AN:

44722

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.0000812

AC:

AN:

86238

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.0000450

AC:

AN:

1111818

Gnomad4 Remaining exome

AF:

0.00286

AC:

173

AN:

60384

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0107

AC:

1626

AN:

152248

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

776

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0375

AC:

0.0375042

AN:

0.0375042

Gnomad4 AMR

AF:

0.00340

AC:

0.00339914

AN:

0.00339914

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000441

AC:

0.0000440995

AN:

0.0000440995

Gnomad4 OTH

AF:

0.00568

AC:

0.00567644

AN:

0.00567644

Heterozygous variant carriers

162

244

325

406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00407

Hom.:

Bravo

AF:

0.0121

ESP6500AA

AF:

0.0352

AC:

155

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00310

AC:

376

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ala26Thr in exon 3 of OSBPL2: This variant is not expected to have clinical si gnificance because it has been identified in 3.52% (364/10354) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs79783838). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.023

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.70

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

MetaRNN

Benign

0.0021

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.86

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

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.090

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

REVEL

Benign

0.033

Sift

Benign

0.34

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

Sift4G

Benign

0.44

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

Polyphen

0.0010, 0.0090

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

Vest4

0.093, 0.12

MVP

0.13

MPC

0.58

ClinPred

0.0026

GERP RS

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.22

Mutation Taster

=90/10

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over