rs136376

Positions:

• chr22-30723513-G-A
• chr22-30723513-G-C

Variant summary

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

The NM_030758.4(OSBP2):​c.645-17648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 151,942 control chromosomes in the GnomAD database, including 59,009 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 0.88 (59009 hom., cov: 30)
• Consequence: OSBP2 NM_030758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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 (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBP2	NM_030758.4	c.645-17648G>A		intron_variant		ENST00000332585.11	NP_110385.1
OSBP2	NM_001282738.2	c.150-17648G>A		intron_variant			NP_001269667.1
OSBP2	NM_001282739.2	c.645-17648G>A		intron_variant			NP_001269668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBP2	ENST00000332585.11	c.645-17648G>A		intron_variant		1	NM_030758.4	ENSP00000332576	A2

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133476 AN: 151820 Hom.: 58941 Cov.: 30

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.853

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.879 AC: 133604 AN: 151942 Hom.: 59009 Cov.: 30 AF XY: 0.883 AC XY: 65621 AN XY: 74278

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.884

Alfa AF: 0.852 Hom.: 6899

Bravo AF: 0.882

Asia WGS AF: 0.978 AC: 3399 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	1.7
DANN	Benign	0.65

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: rs136376; hg19: chr22-31119500;