Variant chr16-83957708-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_182981.3(OSGIN1):c.37A>C(p.Ser13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,605,106 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 18 hom. )

Consequence

OSGIN1
NM_182981.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.481

Variant links:

Genes affected

OSGIN1 (HGNC:30093): (oxidative stress induced growth inhibitor 1) This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]

OSGIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003748864).

BP6

Variant 16-83957708-A-C is Benign according to our data. Variant chr16-83957708-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 782018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSGIN1	NM_182981.3 linkuse as main transcript	c.37A>C	p.Ser13Arg	missense_variant	2/6	ENST00000393306.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGIN1	ENST00000393306.6 linkuse as main transcript	c.37A>C	p.Ser13Arg	missense_variant	2/6	1	NM_182981.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

647

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00688

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00587

Gnomad OTH

AF:

0.00816

GnomAD3 exomes

AF:

0.00405

AC:

940

AN:

232104

Hom.:

AF XY:

0.00427

AC XY:

538

AN XY:

126048

show subpopulations

Gnomad AFR exome

AF:

0.000759

Gnomad AMR exome

AF:

0.00328

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.000979

Gnomad NFE exome

AF:

0.00546

Gnomad OTH exome

AF:

0.00544

GnomAD4 exome

AF:

0.00483

AC:

7022

AN:

1452990

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

3509

AN XY:

722152

show subpopulations

Gnomad4 AFR exome

AF:

0.000632

Gnomad4 AMR exome

AF:

0.00383

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.00525

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.00425

AC:

647

AN:

152116

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

301

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00688

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.00807

Alfa

AF:

0.00587

Hom.:

Bravo

AF:

0.00415

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000911

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00363

AC:

438

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	OSGIN1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.30

MetaRNN

Benign

0.0037

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

N;N;N;.;N

REVEL

Benign

0.0090

Sift

Uncertain

0.0080

D;D;D;.;D

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.14

.;B;.;.;.

Vest4

0.38

MutPred

0.31

.;Gain of solvent accessibility (P = 0.005);.;.;.;

MVP

0.48

MPC

0.10

ClinPred

0.0080

GERP RS

0.50

Varity_R

0.064

gMVP

0.45

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