chr22-30741268-G-C

Position:

• chr22-30741268-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_030758.4(OSBP2):​c.752G>C​(p.Ser251Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBP2 NM_030758.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.58

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096723676).
• BP6: Variant 22-30741268-G-C is Benign according to our data. Variant chr22-30741268-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2245567.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBP2	NM_030758.4	c.752G>C	p.Ser251Thr	missense_variant	2/14	ENST00000332585.11	NP_110385.1
OSBP2	NM_001282739.2	c.752G>C	p.Ser251Thr	missense_variant	2/14		NP_001269668.1
OSBP2	NM_001282738.2	c.257G>C	p.Ser86Thr	missense_variant	3/15		NP_001269667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBP2	ENST00000332585.11	c.752G>C	p.Ser251Thr	missense_variant	2/14	1	NM_030758.4	ENSP00000332576.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.5
DANN	Benign	0.80
DEOGEN2	Benign	0.0023	.;T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.1	.;.;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.4	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.22
MutPred		0.32		.;.;Loss of disorder (P = 0.0657);Loss of disorder (P = 0.0657);
MVP		0.51
MPC		0.50
ClinPred		0.35	T
GERP RS		1.9
Varity_R		0.045
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-31137255;