rs10489546

Variant names:

• chr1-51756042-T-C
• rs10489546
• NM_024586.6:c.544-278T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

OSBPL9 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OSBPL9	NM_024586.6	c.544-278T>C		intron_variant	Intron 8 of 23	ENST00000428468.6	NP_078862.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL9	ENST00000428468.6	c.544-278T>C		intron_variant	Intron 8 of 23	1	NM_024586.6	ENSP00000407168.1

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

African (AFR) AF: 0.458 AC: 19001 AN: 41462

American (AMR) AF: 0.189 AC: 2894 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3470

East Asian (EAS) AF: 0.117 AC: 605 AN: 5176

South Asian (SAS) AF: 0.122 AC: 586 AN: 4816

European-Finnish (FIN) AF: 0.0930 AC: 987 AN: 10614

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10739 AN: 68008

Other (OTH) AF: 0.246 AC: 519 AN: 2114

Alfa AF: 0.197 Hom.: 5421

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
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10489546; hg19: chr1-52221714;