chr20-62260019-G-A

Position:

chr20-62260019-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000313733.9(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. 14/20 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
ENST00000313733.9 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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1626 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OSBPL2	NM_144498.4 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	3/14	ENST00000313733.9	NP_653081.1
OSBPL2	NM_014835.5 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant, splice_region_variant	3/14		NP_055650.1
OSBPL2	NM_001363878.2 linkuse as main transcript	c.-291G>A		5_prime_UTR_variant	3/15		NP_001350807.1
OSBPL2	NM_001278649.3 linkuse as main transcript	c.-184-3597G>A		intron_variant			NP_001265578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	3/14	1	NM_144498.4	ENSP00000316649	P1	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

GnomAD3 exomes

AF:

0.00268

AC:

675

AN:

251410

Hom.:

AF XY:

0.00204

AC XY:

277

AN XY:

135892

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 SAS exome

AF:

0.0000327

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

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00286

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

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00178

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 25, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

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

MutationTaster

Benign

1.0

D;N;N

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

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