chr12-112919404-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.1054G>A(p.Ala352Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,602,930 control chromosomes in the GnomAD database, including 374,330 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43990 hom., cov: 33)

Exomes 𝑓: 0.67 ( 330340 hom. )

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.117

Publications

55 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=1.1934328E-6).

BP6

Variant 12-112919404-G-A is Benign according to our data. Variant chr12-112919404-G-A is described in ClinVar as Benign. ClinVar VariationId is 1167216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_016816.4 link	c.1054G>A	p.Ala352Thr	missense_variant	Exon 6 of 6	ENST00000202917.10	NP_058132.2	P00973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10 link	c.1054G>A	p.Ala352Thr	missense_variant	Exon 6 of 6	1	NM_016816.4	ENSP00000202917.5		P00973-1

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

114022

AN:

152074

Hom.:

43924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.728

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.705

GnomAD2 exomes

AF:

0.715

AC:

178817

AN:

250208

AF XY:

0.704

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.507

Gnomad EAS exome

AF:

0.787

Gnomad FIN exome

AF:

0.738

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.670

AC:

971906

AN:

1450738

Hom.:

330340

Cov.:

AF XY:

0.669

AC XY:

483124

AN XY:

722192

show subpopulations

African (AFR)

AF:

0.941

AC:

31483

AN:

33452

American (AMR)

AF:

0.820

AC:

36643

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

13320

AN:

26014

East Asian (EAS)

AF:

0.796

AC:

31555

AN:

39624

South Asian (SAS)

AF:

0.693

AC:

59548

AN:

85954

European-Finnish (FIN)

AF:

0.730

AC:

38958

AN:

53380

Middle Eastern (MID)

AF:

0.581

AC:

3342

AN:

5752

European-Non Finnish (NFE)

AF:

0.651

AC:

717099

AN:

1101818

Other (OTH)

AF:

0.666

AC:

39958

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

14324

28648

42971

57295

71619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18758

37516

56274

75032

93790

<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:

0.750

AC:

114152

AN:

152192

Hom.:

43990

Cov.:

AF XY:

0.752

AC XY:

55991

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.930

AC:

38630

AN:

41544

American (AMR)

AF:

0.767

AC:

11726

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1737

AN:

3472

East Asian (EAS)

AF:

0.774

AC:

3996

AN:

5164

South Asian (SAS)

AF:

0.709

AC:

3419

AN:

4824

European-Finnish (FIN)

AF:

0.728

AC:

7703

AN:

10584

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.657

AC:

44654

AN:

68002

Other (OTH)

AF:

0.708

AC:

1493

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1376

2753

4129

5506

6882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.680

Hom.:

135179

Bravo

AF:

0.763

TwinsUK

AF:

0.644

AC:

2388

ALSPAC

AF:

0.660

AC:

2543

ESP6500AA

AF:

0.923

AC:

4067

ESP6500EA

AF:

0.646

AC:

5555

ExAC

AF:

0.716

AC:

86959

Asia WGS

AF:

0.767

AC:

2666

AN:

3478

EpiCase

AF:

0.638

EpiControl

AF:

0.644

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 89. 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

0.071

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.21

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.44

T;.

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PhyloP100

-0.12

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.26

N;.

REVEL

Benign

0.018

Sift

Benign

0.51

T;.

Sift4G

Benign

0.24

T;.

Polyphen

0.0020

B;.

Vest4

0.034

ClinPred

0.0058

GERP RS

-1.4

Varity_R

0.055

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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