Genetic Variant OSBPL3:p.Ile827Leu (chr7-24804403-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015550.4(OSBPL3):c.2479A>T(p.Ile827Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I827V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OSBPL3
NM_015550.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.612

Publications

0 publications found

Variant links:

Genes affected

OSBPL3 (HGNC:16370): (oxysterol binding protein like 3) 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. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

OSBPL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04178199).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSBPL3	NM_015550.4	MANE Select	c.2479A>T	p.Ile827Leu	missense	Exon 22 of 23	NP_056365.1	Q9H4L5-1
OSBPL3	NM_145320.2		c.2386A>T	p.Ile796Leu	missense	Exon 20 of 21	NP_663160.1	Q9H4L5-2
OSBPL3	NM_145321.2		c.2371A>T	p.Ile791Leu	missense	Exon 20 of 21	NP_663161.1	Q9H4L5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSBPL3	ENST00000313367.7	TSL:1 MANE Select	c.2479A>T	p.Ile827Leu	missense	Exon 22 of 23	ENSP00000315410.2	Q9H4L5-1
OSBPL3	ENST00000396431.5	TSL:1	c.2386A>T	p.Ile796Leu	missense	Exon 20 of 21	ENSP00000379708.1	Q9H4L5-2
OSBPL3	ENST00000396429.5	TSL:1	c.2371A>T	p.Ile791Leu	missense	Exon 20 of 21	ENSP00000379706.1	Q9H4L5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111946

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.022

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.69

M_CAP

Benign

0.0049

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.61

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.11

REVEL

Benign

0.021

Sift

Benign

0.21

Sift4G

Benign

0.22

Polyphen

0.0030

Vest4

0.24

MutPred

0.30

Loss of methylation at K829 (P = 0.0573)

MVP

0.13

MPC

0.21

ClinPred

0.037

GERP RS

-7.8

Varity_R

0.17

gMVP

0.28

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over