Variant 22-30695318-C-T 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_030758.4(OSBP2):c.409C>T(p.Leu137Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,538 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 9 hom., cov: 33)

Exomes 𝑓: 0.010 ( 95 hom. )

Consequence

OSBP2
NM_030758.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.90

Variant links:

Genes affected

OSBP2 (HGNC:8504): (oxysterol binding protein 2) The protein encoded by this gene contains a pleckstrin homology (PH) domain and an oxysterol-binding region. It binds oxysterols such as 7-ketocholesterol and may inhibit their cytotoxicity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2013]

OSBP2 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=0.003906995).

BP6

Variant 22-30695318-C-T is Benign according to our data. Variant chr22-30695318-C-T is described in ClinVar as [Benign]. Clinvar id is 788839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBP2	NM_030758.4 linkuse as main transcript	c.409C>T	p.Leu137Phe	missense_variant	1/14	ENST00000332585.11	NP_110385.1	Q969R2-1
OSBP2	NM_001282739.2 linkuse as main transcript	c.409C>T	p.Leu137Phe	missense_variant	1/14		NP_001269668.1	Q969R2-2
OSBP2	NM_001282738.2 linkuse as main transcript	c.149+974C>T		intron_variant			NP_001269667.1	Q969R2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBP2	ENST00000332585.11 linkuse as main transcript	c.409C>T	p.Leu137Phe	missense_variant	1/14	1	NM_030758.4	ENSP00000332576.6		Q969R2-1

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

1120

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00666

AC:

1654

AN:

248422

Hom.:

AF XY:

0.00702

AC XY:

948

AN XY:

135016

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00940

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00645

GnomAD4 exome

AF:

0.0103

AC:

15013

AN:

1461230

Hom.:

Cov.:

AF XY:

0.00986

AC XY:

7171

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00196

Gnomad4 FIN exome

AF:

0.00904

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00833

GnomAD4 genome

AF:

0.00735

AC:

1120

AN:

152308

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00985

Hom.:

Bravo

AF:

0.00642

TwinsUK

AF:

0.0162

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.000754

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00675

AC:

816

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

0.064

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.92

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.017

Sift

Benign

0.10

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0

B;.

Vest4

0.057

MVP

0.14

MPC

0.60

ClinPred

0.0017

GERP RS

-4.9

Varity_R

0.048

gMVP

0.076

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