Variant 11-3092466-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020896.4(OSBPL5):c.2225C>T(p.Thr742Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,577,678 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 20 hom. )

Consequence

OSBPL5
NM_020896.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

OSBPL5 (HGNC:16392): (oxysterol binding protein like 5) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

OSBPL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049589574).

BP6

Variant 11-3092466-G-A is Benign according to our data. Variant chr11-3092466-G-A is described in ClinVar as [Benign]. Clinvar id is 716967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-3092466-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL5	NM_020896.4 linkuse as main transcript	c.2225C>T	p.Thr742Ile	missense_variant	19/22	ENST00000263650.12	NP_065947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL5	ENST00000263650.12 linkuse as main transcript	c.2225C>T	p.Thr742Ile	missense_variant	19/22	1	NM_020896.4	ENSP00000263650	P1	Q9H0X9-1

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

524

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00442

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00555

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00392

AC:

733

AN:

186998

Hom.:

AF XY:

0.00374

AC XY:

377

AN XY:

100728

show subpopulations

Gnomad AFR exome

AF:

0.000723

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00185

Gnomad FIN exome

AF:

0.00632

Gnomad NFE exome

AF:

0.00571

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00410

AC:

5850

AN:

1425498

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

2820

AN XY:

706000

show subpopulations

Gnomad4 AFR exome

AF:

0.000673

Gnomad4 AMR exome

AF:

0.00328

Gnomad4 ASJ exome

AF:

0.000236

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00618

Gnomad4 NFE exome

AF:

0.00454

Gnomad4 OTH exome

AF:

0.00438

GnomAD4 genome

AF:

0.00343

AC:

522

AN:

152180

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00442

Gnomad4 NFE

AF:

0.00555

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00503

Hom.:

Bravo

AF:

0.00318

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00420

AC:

ExAC

AF:

0.00364

AC:

435

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;.;T;.;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.053

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.83

T;T;.;T;T;T

MetaRNN

Benign

0.0050

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

.;M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.9

D;D;D;D;D;D

REVEL

Benign

0.097

Sift

Uncertain

0.0050

D;D;D;D;D;D

Sift4G

Benign

0.078

T;T;D;D;T;D

Polyphen

0.90

.;P;.;.;.;.

Vest4

0.33

MVP

0.68

MPC

0.29

ClinPred

0.039

GERP RS

4.5

Varity_R

0.24

gMVP

0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over