Genetic Variant OSBPL2:c.37+23G>A (chr20-62256244-G-A) – ACMG Classification: Benign (-20 pts)

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.37+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,610,548 control chromosomes in the GnomAD database, including 692,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 57354 hom., cov: 32)

Exomes 𝑓: 0.93 ( 635345 hom. )

Consequence

OSBPL2
NM_144498.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00500

Publications

13 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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=-0.91).

BP6

Variant 20-62256244-G-A is Benign according to our data. Variant chr20-62256244-G-A is described in ClinVar as Benign. ClinVar VariationId is 1290984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144498.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OSBPL2	NM_144498.4	MANE Select	c.37+23G>A	intron	N/A	NP_653081.1	Q9H1P3-1
OSBPL2	NM_014835.5		c.37+23G>A	intron	N/A	NP_055650.1	Q9H1P3-2
OSBPL2	NM_001363878.2		c.-330+23G>A	intron	N/A	NP_001350807.1	A0A2R8YDU7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OSBPL2	ENST00000313733.9	TSL:1 MANE Select	c.37+23G>A	intron	N/A	ENSP00000316649.3	Q9H1P3-1
OSBPL2	ENST00000358053.3	TSL:1	c.37+23G>A	intron	N/A	ENSP00000350755.2	Q9H1P3-2
OSBPL2	ENST00000865094.1		c.37+23G>A	intron	N/A	ENSP00000535153.1

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131015

AN:

152058

Hom.:

57331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.932

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.946

Gnomad OTH

AF:

0.895

GnomAD2 exomes

AF:

0.902

AC:

226175

AN:

250684

AF XY:

0.904

show subpopulations

Gnomad AFR exome

AF:

0.691

Gnomad AMR exome

AF:

0.899

Gnomad ASJ exome

AF:

0.929

Gnomad EAS exome

AF:

0.995

Gnomad FIN exome

AF:

0.859

Gnomad NFE exome

AF:

0.943

Gnomad OTH exome

AF:

0.909

GnomAD4 exome

AF:

0.932

AC:

1358957

AN:

1458372

Hom.:

635345

Cov.:

AF XY:

0.930

AC XY:

674782

AN XY:

725742

show subpopulations

African (AFR)

AF:

0.681

AC:

22709

AN:

33330

American (AMR)

AF:

0.897

AC:

39944

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.931

AC:

24282

AN:

26092

East Asian (EAS)

AF:

0.991

AC:

39336

AN:

39676

South Asian (SAS)

AF:

0.836

AC:

71999

AN:

86140

European-Finnish (FIN)

AF:

0.858

AC:

45741

AN:

53308

Middle Eastern (MID)

AF:

0.886

AC:

5098

AN:

5754

European-Non Finnish (NFE)

AF:

0.951

AC:

1054464

AN:

1109350

Other (OTH)

AF:

0.920

AC:

55384

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4200

8399

12599

16798

20998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21510

43020

64530

86040

107550

<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:

0.861

AC:

131092

AN:

152176

Hom.:

57354

Cov.:

AF XY:

0.857

AC XY:

63754

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.699

AC:

28992

AN:

41482

American (AMR)

AF:

0.870

AC:

13301

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.932

AC:

3235

AN:

3472

East Asian (EAS)

AF:

0.992

AC:

5121

AN:

5162

South Asian (SAS)

AF:

0.828

AC:

3993

AN:

4822

European-Finnish (FIN)

AF:

0.854

AC:

9056

AN:

10604

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.946

AC:

64367

AN:

68018

Other (OTH)

AF:

0.896

AC:

1894

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

858

1716

2574

3432

4290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.917

Hom.:

49759

Bravo

AF:

0.859

Asia WGS

AF:

0.899

AC:

3125

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Autosomal dominant nonsyndromic hearing loss 67 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

(source)

DANN

Benign

0.62

PhyloP100

-0.0050

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over