1-51769069-T-A

Variant names:

• chr1-51769069-T-A
• rs768529
• NM_024586.6:c.939-3001T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024586.6(OSBPL9):​c.939-3001T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,074 control chromosomes in the GnomAD database, including 13,004 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 0.39 (13004 hom., cov: 31)
• Consequence: OSBPL9 NM_024586.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL9	NM_024586.6	c.939-3001T>A		intron_variant	Intron 12 of 23	ENST00000428468.6	NP_078862.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL9	ENST00000428468.6	c.939-3001T>A		intron_variant	Intron 12 of 23	1	NM_024586.6	ENSP00000407168.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59732 AN: 151956 Hom.: 12994 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.393 AC: 59749 AN: 152074 Hom.: 13004 Cov.: 31 AF XY: 0.397 AC XY: 29534 AN XY: 74326

African (AFR) AF: 0.249 AC: 10350 AN: 41504

American (AMR) AF: 0.533 AC: 8145 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3466

East Asian (EAS) AF: 0.835 AC: 4318 AN: 5170

South Asian (SAS) AF: 0.456 AC: 2196 AN: 4818

European-Finnish (FIN) AF: 0.353 AC: 3729 AN: 10566

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28415 AN: 67968

Other (OTH) AF: 0.414 AC: 874 AN: 2110

Alfa AF: 0.386 Hom.: 1455

Bravo AF: 0.403

Asia WGS AF: 0.612 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.59
PhyloP100		0.41
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: rs768529; hg19: chr1-52234741;