Variant 11-59594258-GT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002556.3(OSBP):c.1312-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,613,786 control chromosomes in the GnomAD database, including 70 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 37 hom. )

Consequence

OSBP
NM_002556.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

OSBP (HGNC:8503): (oxysterol binding protein) Oxysterol binding protein is an intracellular protein that is believed to transport sterols from lysosomes to the nucleus where the sterol down-regulates the genes for the LDL receptor, HMG-CoA reductase, and HMG synthetase [provided by RefSeq, Jul 2008]

OSBP links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 11-59594258-GT-G is Benign according to our data. Variant chr11-59594258-GT-G is described in ClinVar as [Benign]. Clinvar id is 780974.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1731/152334) while in subpopulation AFR AF= 0.0399 (1660/41570). AF 95% confidence interval is 0.0383. There are 33 homozygotes in gnomad4. There are 830 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1731 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSBP	NM_002556.3 linkuse as main transcript	c.1312-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263847.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
OSBP	ENST00000263847.6 linkuse as main transcript	c.1312-4del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_002556.3	P1
OSBP	ENST00000525357.1 linkuse as main transcript	c.171-4del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	1
	ENST00000661394.1 linkuse as main transcript	n.401+18140del	intron_variant, non_coding_transcript_variant
OSBP	ENST00000528903.1 linkuse as main transcript	n.98-4del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1730

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00285

AC:

714

AN:

250964

Hom.:

AF XY:

0.00223

AC XY:

302

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.0401

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00116

AC:

1690

AN:

1461452

Hom.:

Cov.:

AF XY:

0.000985

AC XY:

716

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.0114

AC:

1731

AN:

152334

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

830

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0399

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000701

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

OSBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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