NM_144498.4:c.66A>G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_144498.4(OSBPL2):c.66A>G(p.Glu22Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
OSBPL2
NM_144498.4 synonymous
NM_144498.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.799
Publications
0 publications found
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 67Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- nonsyndromic genetic hearing lossInheritance: AD Classification: MODERATE Submitted by: ClinGen
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 20-62260009-A-G is Benign according to our data. Variant chr20-62260009-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2707660.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.799 with no splicing effect.
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OSBPL2 | NM_144498.4 | MANE Select | c.66A>G | p.Glu22Glu | synonymous | Exon 3 of 14 | NP_653081.1 | Q9H1P3-1 | |
| OSBPL2 | NM_001363878.2 | c.-301A>G | 5_prime_UTR | Exon 3 of 15 | NP_001350807.1 | A0A2R8YDU7 | |||
| OSBPL2 | NM_014835.5 | c.38-8A>G | splice_region intron | N/A | NP_055650.1 | Q9H1P3-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OSBPL2 | ENST00000313733.9 | TSL:1 MANE Select | c.66A>G | p.Glu22Glu | synonymous | Exon 3 of 14 | ENSP00000316649.3 | Q9H1P3-1 | |
| OSBPL2 | ENST00000358053.3 | TSL:1 | c.38-8A>G | splice_region intron | N/A | ENSP00000350755.2 | Q9H1P3-2 | ||
| OSBPL2 | ENST00000865094.1 | c.66A>G | p.Glu22Glu | synonymous | Exon 3 of 14 | ENSP00000535153.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152116
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152116
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74332
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41420
American (AMR)
AF:
AC:
0
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68030
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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