rs2297592

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:5

Conservation

PhyloP100: -1.80

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 67
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 (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 VariationId 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	Exon rank	MANE	Protein
OSBPL2	NM_144498.4 link	c.1125+15A>G	intron_variant	Intron 11 of 13	ENST00000313733.9	NP_653081.1
OSBPL2	NM_014835.5 link	c.1089+15A>G	intron_variant	Intron 11 of 13		NP_055650.1
OSBPL2	NM_001363878.2 link	c.849+15A>G	intron_variant	Intron 12 of 14		NP_001350807.1
OSBPL2	NM_001278649.3 link	c.849+15A>G	intron_variant	Intron 11 of 12		NP_001265578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9 link	c.1125+15A>G		intron_variant	Intron 11 of 13	1	NM_144498.4	ENSP00000316649.3

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

GnomAD2 exomes

AF:

0.433

AC:

107676

AN:

248534

AF XY:

0.434

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 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

African (AFR)

AF:

0.450

AC:

14993

AN:

33304

American (AMR)

AF:

0.372

AC:

16533

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

12194

AN:

25952

East Asian (EAS)

AF:

0.445

AC:

17554

AN:

39414

South Asian (SAS)

AF:

0.389

AC:

33396

AN:

85960

European-Finnish (FIN)

AF:

0.407

AC:

21097

AN:

51848

Middle Eastern (MID)

AF:

0.456

AC:

2502

AN:

5482

European-Non Finnish (NFE)

AF:

0.466

AC:

515070

AN:

1104120

Other (OTH)

AF:

0.453

AC:

27100

AN:

59830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

17960

35920

53881

71841

89801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15438

30876

46314

61752

77190

<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:

0.440

AC:

66922

AN:

152144

Hom.:

14774

Cov.:

AF XY:

0.433

AC XY:

32229

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.450

AC:

18690

AN:

41510

American (AMR)

AF:

0.386

AC:

5900

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1657

AN:

3472

East Asian (EAS)

AF:

0.455

AC:

2357

AN:

5184

South Asian (SAS)

AF:

0.370

AC:

1785

AN:

4824

European-Finnish (FIN)

AF:

0.396

AC:

4186

AN:

10574

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.455

AC:

30933

AN:

67968

Other (OTH)

AF:

0.450

AC:

951

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2000

4000

6001

8001

10001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.456

Hom.:

3539

Bravo

AF:

0.442

Asia WGS

AF:

0.365

AC:

1270

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.93

(source)

DANN

Benign

0.27

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over