22-30809347-T-C

Variant names:

• chr22-30809347-T-C
• rs4444
• NM_030758.4:c.854-61082T>C

Variant summary

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

The NM_030758.4(OSBP2):​c.854-61082T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,014 control chromosomes in the GnomAD database, including 19,561 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 (19561 hom., cov: 31)
• Consequence: OSBP2 NM_030758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 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.854-61082T>C		intron	N/A	NP_110385.1	Q969R2-1
	OSBP2	NM_001282739.2		c.854-61082T>C		intron	N/A	NP_001269668.1	Q969R2-2
	OSBP2	NM_001282738.2		c.359-61082T>C		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.854-61082T>C		intron	N/A	ENSP00000332576.6	Q969R2-1
	OSBP2	ENST00000446658.6	TSL:1	c.854-61082T>C		intron	N/A	ENSP00000392080.2	Q969R2-2
	OSBP2	ENST00000915561.1		c.854-61082T>C		intron	N/A	ENSP00000585620.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75137 AN: 151896 Hom.: 19534 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.495 AC: 75219 AN: 152014 Hom.: 19561 Cov.: 31 AF XY: 0.487 AC XY: 36199 AN XY: 74286

African (AFR) AF: 0.660 AC: 27392 AN: 41476

American (AMR) AF: 0.349 AC: 5335 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1699 AN: 5162

South Asian (SAS) AF: 0.375 AC: 1805 AN: 4810

European-Finnish (FIN) AF: 0.455 AC: 4798 AN: 10556

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31411 AN: 67950

Other (OTH) AF: 0.477 AC: 1004 AN: 2104

Alfa AF: 0.462 Hom.: 69590

Bravo AF: 0.493

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.099
DANN	Benign	0.24
PhyloP100		-1.2
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: rs4444; hg19: chr22-31205334;