rs10489546

Positions:

• chr1-51756042-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024586.6(OSBPL9):​c.544-278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,164 control chromosomes in the GnomAD database, including 6,041 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (6041 hom., cov: 32)
• Consequence: OSBPL9 NM_024586.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

Genes affected

OSBPL9 (HGNC:16386): (oxysterol binding protein like 9) 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 some members contain only the sterol-binding domain. This family member functions as a cholesterol transfer protein that regulates Golgi structure and function. Multiple transcript variants, most of which encode distinct isoforms, have been identified. Related pseudogenes have been identified on chromosomes 3, 11 and 12. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL9	NM_024586.6	c.544-278T>C		intron_variant		ENST00000428468.6	NP_078862.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL9	ENST00000428468.6	c.544-278T>C		intron_variant		1	NM_024586.6	ENSP00000407168	P4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36545 AN: 152046 Hom.: 6008 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.249

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36624 AN: 152164 Hom.: 6041 Cov.: 32 AF XY: 0.234 AC XY: 17424 AN XY: 74410

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.246

Alfa AF: 0.186 Hom.: 3216

Bravo AF: 0.261

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.44

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: rs10489546; hg19: chr1-52221714;