Genetic Variant OSBPL2:c.38-227_38-209delACTGGAGCTCGCTGGGAGC (chr20-62259751-GGCACTGGAGCTCGCTGGGA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_144498.4(OSBPL2):c.38-227_38-209delACTGGAGCTCGCTGGGAGC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12805 hom., cov: 0)

Consequence

OSBPL2
NM_144498.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.894

Publications

0 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 -10 ACMG points.

BP6

Variant 20-62259751-GGCACTGGAGCTCGCTGGGA-G is Benign according to our data. Variant chr20-62259751-GGCACTGGAGCTCGCTGGGA-G is described in ClinVar as Benign. ClinVar VariationId is 1259404.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 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.38-227_38-209delACTGGAGCTCGCTGGGAGC	intron	N/A	NP_653081.1	Q9H1P3-1
OSBPL2	NM_014835.5		c.38-263_38-245delACTGGAGCTCGCTGGGAGC	intron	N/A	NP_055650.1	Q9H1P3-2
OSBPL2	NM_001363878.2		c.-329-227_-329-209delACTGGAGCTCGCTGGGAGC	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.38-229_38-211delGCACTGGAGCTCGCTGGGA	intron	N/A	ENSP00000316649.3	Q9H1P3-1
OSBPL2	ENST00000358053.3	TSL:1	c.38-265_38-247delGCACTGGAGCTCGCTGGGA	intron	N/A	ENSP00000350755.2	Q9H1P3-2
OSBPL2	ENST00000865094.1		c.38-229_38-211delGCACTGGAGCTCGCTGGGA	intron	N/A	ENSP00000535153.1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58528

AN:

151880

Hom.:

12810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.385

AC:

58540

AN:

151998

Hom.:

12805

Cov.:

AF XY:

0.387

AC XY:

28760

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.150

AC:

6214

AN:

41518

American (AMR)

AF:

0.471

AC:

7180

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1706

AN:

3466

East Asian (EAS)

AF:

0.523

AC:

2687

AN:

5136

South Asian (SAS)

AF:

0.473

AC:

2275

AN:

4814

European-Finnish (FIN)

AF:

0.429

AC:

4541

AN:

10578

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.477

AC:

32399

AN:

67926

Other (OTH)

AF:

0.420

AC:

886

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1605

3210

4816

6421

8026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.416

Hom.:

1717

Bravo

AF:

0.379

Asia WGS

AF:

0.519

AC:

1805

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over