rs148909045

Variant names:

• chr1-51746715-T-G
• rs148909045
• ENST00000462759.5:c.-76T>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001330580.2(OSBPL9):​c.-76T>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000427 in 1,608,382 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: OSBPL9 NM_001330580.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.01
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27594197).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330580.2. 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.420T>G	p.Phe140Leu	missense	Exon 6 of 24	NP_078862.4
	OSBPL9	NM_001330580.2		c.-76T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 21	NP_001317509.1	Q96SU4-4
	OSBPL9	NM_148904.4		c.-76T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 20	NP_683702.1	Q96SU4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL9	ENST00000462759.5	TSL:1	c.-76T>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 20	ENSP00000433279.1	Q96SU4-5
	OSBPL9	ENST00000428468.6	TSL:1 MANE Select	c.420T>G	p.Phe140Leu	missense	Exon 6 of 24	ENSP00000407168.1	Q96SU4-1
	OSBPL9	ENST00000453295.5	TSL:1	c.369T>G	p.Phe123Leu	missense	Exon 5 of 23	ENSP00000413263.1	Q96SU4-7

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000173 AC: 43 AN: 248420 AF XY: 0.000186

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000363

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000448 AC: 652 AN: 1456156 Hom.: 1 Cov.: 29 AF XY: 0.000424 AC XY: 307 AN XY: 724558

African (AFR) AF: 0.0000602 AC: 2 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.00 AC: 0 AN: 85340

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000541 AC: 600 AN: 1108944

Other (OTH) AF: 0.000798 AC: 48 AN: 60138

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74370

African (AFR) AF: 0.0000724 AC: 3 AN: 41454

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000298 Hom.: 0

Bravo AF: 0.000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.000383

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.38	N
REVEL	Benign	0.19
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.99	D
Vest4		0.72
MVP		0.45
MPC		0.11
ClinPred		0.098	T
GERP RS		4.7
Varity_R		0.26
gMVP		0.37
Mutation Taster		=276/24	polymorphism

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: rs148909045; hg19: chr1-52212387;