rs2297592

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144498.4(OSBPL2):c.1125+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,602,472 control chromosomes in the GnomAD database, including 166,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14774 hom., cov: 33)

Exomes 𝑓: 0.46 ( 151457 hom. )

Consequence

OSBPL2
NM_144498.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.80

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 (BayesDel_noAF=-0.99).

BP6

Variant 20-62286726-A-G is Benign according to our data. Variant chr20-62286726-A-G is described in ClinVar as [Benign]. Clinvar id is 517559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
OSBPL2	NM_144498.4 linkuse as main transcript	c.1125+15A>G	intron_variant	ENST00000313733.9
OSBPL2	NM_001278649.3 linkuse as main transcript	c.849+15A>G	intron_variant
OSBPL2	NM_001363878.2 linkuse as main transcript	c.849+15A>G	intron_variant
OSBPL2	NM_014835.5 linkuse as main transcript	c.1089+15A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSBPL2	ENST00000313733.9 linkuse as main transcript	c.1125+15A>G		intron_variant		1	NM_144498.4	P1	Q9H1P3-1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66872

AN:

152026

Hom.:

14769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.454

GnomAD3 exomes

AF:

0.433

AC:

107676

AN:

248534

Hom.:

23566

AF XY:

0.434

AC XY:

58319

AN XY:

134508

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.368

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.472

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.400

Gnomad NFE exome

AF:

0.461

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.455

AC:

660439

AN:

1450328

Hom.:

151457

Cov.:

AF XY:

0.454

AC XY:

326456

AN XY:

719422

show subpopulations

Gnomad4 AFR exome

AF:

0.450

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.470

Gnomad4 EAS exome

AF:

0.445

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.466

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.440

AC:

66922

AN:

152144

Hom.:

14774

Cov.:

AF XY:

0.433

AC XY:

32229

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.450

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.477

Gnomad4 EAS

AF:

0.455

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.456

Hom.:

3462

Bravo

AF:

0.442

Asia WGS

AF:

0.365

AC:

1270

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

c.1125+15A>G in intron 11 of OSBPL2: This variant is not expected to have clinic al significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 47.57% (4077/85 70) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs2297592). -

Autosomal dominant nonsyndromic hearing loss 67

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

Cadd

Benign

0.93

Dann

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over