rs7524425

Variant names:

• chr1-51686435-G-C
• rs7524425
• NM_024586.6:c.241+16923G>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.241+16923G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,956 control chromosomes in the GnomAD database, including 6,114 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 (6114 hom., cov: 32)
• Consequence: OSBPL9 NM_024586.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024586.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL9	NM_024586.6	MANE Select	c.241+16923G>C		intron	N/A	NP_078862.4
	OSBPL9	NM_001416292.1		c.295+16923G>C		intron	N/A	NP_001403221.1
	OSBPL9	NM_001416293.1		c.295+16923G>C		intron	N/A	NP_001403222.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL9	ENST00000428468.6	TSL:1 MANE Select	c.241+16923G>C		intron	N/A	ENSP00000407168.1	Q96SU4-1
	OSBPL9	ENST00000453295.5	TSL:1	c.190+16923G>C		intron	N/A	ENSP00000413263.1	Q96SU4-7
	OSBPL9	ENST00000930350.1		c.241+16923G>C		intron	N/A	ENSP00000600409.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36684 AN: 151838 Hom.: 6081 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.242 AC: 36763 AN: 151956 Hom.: 6114 Cov.: 32 AF XY: 0.235 AC XY: 17486 AN XY: 74282

African (AFR) AF: 0.462 AC: 19122 AN: 41382

American (AMR) AF: 0.190 AC: 2896 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3468

East Asian (EAS) AF: 0.117 AC: 604 AN: 5158

South Asian (SAS) AF: 0.122 AC: 590 AN: 4826

European-Finnish (FIN) AF: 0.0943 AC: 996 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10737 AN: 67958

Other (OTH) AF: 0.248 AC: 525 AN: 2114

Alfa AF: 0.193 Hom.: 537

Bravo AF: 0.263

Asia WGS AF: 0.160 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.68
PhyloP100		-1.3
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: rs7524425; hg19: chr1-52152107;