Variant chr22-30694984-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_030758.4(OSBP2):c.75G>C(p.Thr25Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,550,992 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 49 hom. )

Consequence

OSBP2
NM_030758.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.919

Variant links:

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]

OSBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 22-30694984-G-C is Benign according to our data. Variant chr22-30694984-G-C is described in ClinVar as [Benign]. Clinvar id is 788933.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2192/151636) while in subpopulation AFR AF= 0.0495 (2055/41520). AF 95% confidence interval is 0.0477. There are 49 homozygotes in gnomad4. There are 1008 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBP2	NM_030758.4 linkuse as main transcript	c.75G>C	p.Thr25Thr	synonymous_variant	1/14	ENST00000332585.11	NP_110385.1	Q969R2-1
OSBP2	NM_001282739.2 linkuse as main transcript	c.75G>C	p.Thr25Thr	synonymous_variant	1/14		NP_001269668.1	Q969R2-2
OSBP2	NM_001282738.2 linkuse as main transcript	c.149+640G>C		intron_variant			NP_001269667.1	Q969R2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBP2	ENST00000332585.11 linkuse as main transcript	c.75G>C	p.Thr25Thr	synonymous_variant	1/14	1	NM_030758.4	ENSP00000332576.6		Q969R2-1

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2193

AN:

151526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0497

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00473

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000622

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00294

AC:

439

AN:

149392

Hom.:

AF XY:

0.00241

AC XY:

200

AN XY:

82886

show subpopulations

Gnomad AFR exome

AF:

0.0417

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000408

Gnomad NFE exome

AF:

0.000359

Gnomad OTH exome

AF:

0.00268

GnomAD4 exome

AF:

0.00161

AC:

2259

AN:

1399356

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

959

AN XY:

692276

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000758

Gnomad4 FIN exome

AF:

0.000286

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.00372

GnomAD4 genome

AF:

0.0145

AC:

2192

AN:

151636

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1008

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.0495

Gnomad4 AMR

AF:

0.00472

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000622

Gnomad4 OTH

AF:

0.0100

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.0169

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over