Variant 20-62256244-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000313733.9(OSBPL2):c.37+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,610,548 control chromosomes in the GnomAD database, including 692,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 57354 hom., cov: 32)

Exomes 𝑓: 0.93 ( 635345 hom. )

Consequence

OSBPL2
ENST00000313733.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00500

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 20-62256244-G-A is Benign according to our data. Variant chr20-62256244-G-A is described in ClinVar as [Benign]. Clinvar id is 1290984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
OSBPL2	NM_144498.4 linkuse as main transcript	c.37+23G>A	intron_variant	ENST00000313733.9	NP_653081.1
OSBPL2	NM_001278649.3 linkuse as main transcript	c.-185+23G>A	intron_variant		NP_001265578.1
OSBPL2	NM_001363878.2 linkuse as main transcript	c.-330+23G>A	intron_variant		NP_001350807.1
OSBPL2	NM_014835.5 linkuse as main transcript	c.37+23G>A	intron_variant		NP_055650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9 linkuse as main transcript	c.37+23G>A		intron_variant		1	NM_144498.4	ENSP00000316649	P1	Q9H1P3-1

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131015

AN:

152058

Hom.:

57331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.932

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.946

Gnomad OTH

AF:

0.895

GnomAD3 exomes

AF:

0.902

AC:

226175

AN:

250684

Hom.:

102805

AF XY:

0.904

AC XY:

122457

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.691

Gnomad AMR exome

AF:

0.899

Gnomad ASJ exome

AF:

0.929

Gnomad EAS exome

AF:

0.995

Gnomad SAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.859

Gnomad NFE exome

AF:

0.943

Gnomad OTH exome

AF:

0.909

GnomAD4 exome

AF:

0.932

AC:

1358957

AN:

1458372

Hom.:

635345

Cov.:

AF XY:

0.930

AC XY:

674782

AN XY:

725742

show subpopulations

Gnomad4 AFR exome

AF:

0.681

Gnomad4 AMR exome

AF:

0.897

Gnomad4 ASJ exome

AF:

0.931

Gnomad4 EAS exome

AF:

0.991

Gnomad4 SAS exome

AF:

0.836

Gnomad4 FIN exome

AF:

0.858

Gnomad4 NFE exome

AF:

0.951

Gnomad4 OTH exome

AF:

0.920

GnomAD4 genome

AF:

0.861

AC:

131092

AN:

152176

Hom.:

57354

Cov.:

AF XY:

0.857

AC XY:

63754

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.699

Gnomad4 AMR

AF:

0.870

Gnomad4 ASJ

AF:

0.932

Gnomad4 EAS

AF:

0.992

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.854

Gnomad4 NFE

AF:

0.946

Gnomad4 OTH

AF:

0.896

Alfa

AF:

0.919

Hom.:

35687

Bravo

AF:

0.859

Asia WGS

AF:

0.899

AC:

3125

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Jun 22, 2018	- -

Autosomal dominant nonsyndromic hearing loss 67

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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