rs9609078

Positions:

• chr22-30757289-G-A
• chr22-30757289-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030758.4(OSBP2):​c.853+15920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,930 control chromosomes in the GnomAD database, including 3,763 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 0.18 (3763 hom., cov: 31)
• Consequence: OSBP2 NM_030758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

Genes affected

OSBP2 (HGNC:8504): (oxysterol binding protein 2) The protein encoded by this gene contains a pleckstrin homology (PH) domain and an oxysterol-binding region. It binds oxysterols such as 7-ketocholesterol and may inhibit their cytotoxicity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSBP2	NM_030758.4	c.853+15920G>A		intron_variant		ENST00000332585.11
OSBP2	NM_001282738.2	c.358+15920G>A		intron_variant
OSBP2	NM_001282739.2	c.853+15920G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSBP2	ENST00000332585.11	c.853+15920G>A		intron_variant		1	NM_030758.4	A2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28028 AN: 151812 Hom.: 3746 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.185 AC: 28088 AN: 151930 Hom.: 3763 Cov.: 31 AF XY: 0.181 AC XY: 13459 AN XY: 74264

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.176

Alfa AF: 0.110 Hom.: 1519

Bravo AF: 0.201

Asia WGS AF: 0.152 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs9609078; hg19: chr22-31153276; COSMIC: COSV60252012;