11-59594000-G-A

Position:

• chr11-59594000-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002556.3(OSBP):​c.1557+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,613,278 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (126 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (128 hom.)
• Consequence: OSBP NM_002556.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.182

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-59594000-G-A is Benign according to our data. Variant chr11-59594000-G-A is described in ClinVar as [Benign]. Clinvar id is 786194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBP	NM_002556.3	c.1557+10C>T		intron_variant		ENST00000263847.6	NP_002547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBP	ENST00000263847.6	c.1557+10C>T		intron_variant		1	NM_002556.3	ENSP00000263847.1
OSBP	ENST00000525357.1	n.414+10C>T		intron_variant		1		ENSP00000432399.1
OSBP	ENST00000528903.1	n.353C>T		non_coding_transcript_exon_variant	2/2	2
ENSG00000255139	ENST00000661394.1	n.401+17881G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3445 AN: 152126 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00569 AC: 1425 AN: 250358 Hom.: 42 AF XY: 0.00407 AC XY: 551 AN XY: 135272

Gnomad AFR exome AF: 0.0783

Gnomad AMR exome AF: 0.00340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00232 AC: 3385 AN: 1461034 Hom.: 128 Cov.: 31 AF XY: 0.00203 AC XY: 1476 AN XY: 726710

Gnomad4 AFR exome AF: 0.0829

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00456

GnomAD4 genome AF: 0.0227 AC: 3454 AN: 152244 Hom.: 126 Cov.: 32 AF XY: 0.0210 AC XY: 1561 AN XY: 74438

Gnomad4 AFR AF: 0.0798

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0173 Hom.: 24

Bravo AF: 0.0258

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Sep 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.3
DANN	Benign	0.85
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

Other links and lift over

dbSNP: rs75820709; hg19: chr11-59361473;