22-30859042-G-T

Variant names:

• chr22-30859042-G-T
• rs5997788
• NM_030758.4:c.854-11387G>T

Variant summary

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

The NM_030758.4(OSBP2):​c.854-11387G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,612 control chromosomes in the GnomAD database, including 19,201 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 0.49 (19201 hom., cov: 30)
• Consequence: OSBP2 NM_030758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030758.4. 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
	OSBP2	NM_030758.4	MANE Select	c.854-11387G>T		intron	N/A	NP_110385.1	Q969R2-1
	OSBP2	NM_001282739.2		c.854-11387G>T		intron	N/A	NP_001269668.1	Q969R2-2
	OSBP2	NM_001282738.2		c.359-11387G>T		intron	N/A	NP_001269667.1	Q969R2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBP2	ENST00000332585.11	TSL:1 MANE Select	c.854-11387G>T		intron	N/A	ENSP00000332576.6	Q969R2-1
	OSBP2	ENST00000446658.6	TSL:1	c.854-11387G>T		intron	N/A	ENSP00000392080.2	Q969R2-2
	OSBP2	ENST00000915561.1		c.854-11387G>T		intron	N/A	ENSP00000585620.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74902 AN: 151494 Hom.: 19190 Cov.: 30

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.494 AC: 74963 AN: 151612 Hom.: 19201 Cov.: 30 AF XY: 0.504 AC XY: 37322 AN XY: 74050

African (AFR) AF: 0.387 AC: 15982 AN: 41262

American (AMR) AF: 0.504 AC: 7681 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1407 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3472 AN: 5142

South Asian (SAS) AF: 0.578 AC: 2756 AN: 4772

European-Finnish (FIN) AF: 0.674 AC: 7075 AN: 10496

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34879 AN: 67926

Other (OTH) AF: 0.469 AC: 985 AN: 2102

Alfa AF: 0.498 Hom.: 16233

Bravo AF: 0.478

Asia WGS AF: 0.629 AC: 2188 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.88
PhyloP100		-0.35
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: rs5997788; hg19: chr22-31255029;