12-112911065-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016816.4(OAS1):c.484G>A(p.Gly162Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,612,274 control chromosomes in the GnomAD database, including 259,474 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20096 hom., cov: 30)

Exomes 𝑓: 0.57 ( 239378 hom. )

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.0220

Publications

96 publications found

Variant links:

Genes affected

OAS1 (HGNC:8086): (2'-5'-oligoadenylate synthetase 1) This interferon-induced gene encodes a protein that synthesizes 2',5'-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12. [provided by RefSeq, May 2022]

OAS1 Gene-Disease associations (from GenCC):

pulmonary alveolar proteinosis with hypogammaglobulinemia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

OAS1 links:

ENSG00000257452 (HGNC:):

ENSG00000257452 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1463453E-5).

BP6

Variant 12-112911065-G-A is Benign according to our data. Variant chr12-112911065-G-A is described in ClinVar as Benign. ClinVar VariationId is 13985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_016816.4 link	c.484G>A	p.Gly162Ser	missense_variant	Exon 3 of 6	ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10 link	c.484G>A	p.Gly162Ser	missense_variant	Exon 3 of 6	1	NM_016816.4	ENSP00000202917.5

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73719

AN:

151706

Hom.:

20085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.498

GnomAD2 exomes

AF:

0.569

AC:

142536

AN:

250300

AF XY:

0.571

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.699

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.579

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.567

AC:

828699

AN:

1460450

Hom.:

239378

Cov.:

AF XY:

0.568

AC XY:

412896

AN XY:

726498

show subpopulations

African (AFR)

AF:

0.205

AC:

6857

AN:

33460

American (AMR)

AF:

0.690

AC:

30810

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

10102

AN:

26106

East Asian (EAS)

AF:

0.622

AC:

24688

AN:

39678

South Asian (SAS)

AF:

0.573

AC:

49289

AN:

86062

European-Finnish (FIN)

AF:

0.624

AC:

33349

AN:

53404

Middle Eastern (MID)

AF:

0.414

AC:

2382

AN:

5758

European-Non Finnish (NFE)

AF:

0.575

AC:

639149

AN:

1110998

Other (OTH)

AF:

0.532

AC:

32073

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

16819

33638

50456

67275

84094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17588

35176

52764

70352

87940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.486

AC:

73751

AN:

151824

Hom.:

20096

Cov.:

AF XY:

0.494

AC XY:

36626

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.228

AC:

9450

AN:

41396

American (AMR)

AF:

0.609

AC:

9291

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1328

AN:

3470

East Asian (EAS)

AF:

0.610

AC:

3128

AN:

5132

South Asian (SAS)

AF:

0.579

AC:

2780

AN:

4800

European-Finnish (FIN)

AF:

0.628

AC:

6626

AN:

10548

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.582

AC:

39548

AN:

67908

Other (OTH)

AF:

0.497

AC:

1048

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1702

3404

5106

6808

8510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.547

Hom.:

60577

Bravo

AF:

0.472

TwinsUK

AF:

0.581

AC:

2153

ALSPAC

AF:

0.588

AC:

2267

ESP6500AA

AF:

0.245

AC:

1081

ESP6500EA

AF:

0.566

AC:

4868

ExAC

AF:

0.562

AC:

68241

Asia WGS

AF:

0.563

AC:

1954

AN:

3478

EpiCase

AF:

0.556

EpiControl

AF:

0.560

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 16014697)

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

OAS1 polymorphism

Uncertain:1

Feb 01, 2006

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 87% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported.

OAS1-related disorder

Benign:1

May 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.025

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.047

T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.061

T;T;T;T;T

MetaRNN

Benign

0.000011

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L;L;.;.

PhyloP100

0.022

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.34

T;T;T;T;T

Sift4G

Benign

0.68

T;T;T;T;T

Vest4

0.048

ClinPred

0.0081

GERP RS

-5.9

Varity_R

0.082

gMVP

0.26

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over