dbSNP rs856600: OSBPL9:c.318+15278C>T (chr1-51729357-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024586.6(OSBPL9):c.318+15278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 152,306 control chromosomes in the GnomAD database, including 878 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 0.088 ( 878 hom., cov: 32)

Exomes 𝑓: 0.061 ( 0 hom. )

Consequence

OSBPL9
NM_024586.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.941

Publications

8 publications found

Variant links:

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

OSBPL9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OSBPL9	NM_024586.6	MANE Select	c.318+15278C>T	intron	N/A	NP_078862.4
OSBPL9	NM_001416292.1		c.372+15278C>T	intron	N/A	NP_001403221.1
OSBPL9	NM_001416293.1		c.372+15278C>T	intron	N/A	NP_001403222.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OSBPL9	ENST00000428468.6	TSL:1 MANE Select	c.318+15278C>T	intron	N/A	ENSP00000407168.1	Q96SU4-1
OSBPL9	ENST00000453295.5	TSL:1	c.267+15278C>T	intron	N/A	ENSP00000413263.1	Q96SU4-7
OSBPL9	ENST00000532975.5	TSL:4	c.-199C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000432801.1	E9PNR1

Frequencies

GnomAD3 genomes

AF:

0.0877

AC:

13335

AN:

152094

Hom.:

867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.0319

Gnomad AMR

AF:

0.0580

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.229

Gnomad SAS

AF:

0.0391

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.0803

GnomAD4 exome

AF:

0.0612

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0349

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0878

AC:

13359

AN:

152208

Hom.:

878

Cov.:

AF XY:

0.0869

AC XY:

6469

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.164

AC:

6830

AN:

41540

American (AMR)

AF:

0.0579

AC:

886

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3468

East Asian (EAS)

AF:

0.229

AC:

1179

AN:

5142

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4826

European-Finnish (FIN)

AF:

0.0338

AC:

359

AN:

10612

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0530

AC:

3601

AN:

67998

Other (OTH)

AF:

0.0908

AC:

192

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

589

1178

1768

2357

2946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0694

Hom.:

1357

Bravo

AF:

0.0948

Asia WGS

AF:

0.177

AC:

613

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.94

(source)

DANN

Benign

0.81

PhyloP100

-0.94

PromoterAI

-0.042

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over