12-112919637-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_001032409.3(OAS1):c.1189G>A(p.Gly397Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,607,450 control chromosomes in the GnomAD database, including 372,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43967 hom., cov: 30)

Exomes 𝑓: 0.67 ( 328925 hom. )

Consequence

OAS1
NM_001032409.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.747

Publications

119 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=9.122781E-7).

BP6

Variant 12-112919637-G-A is Benign according to our data. Variant chr12-112919637-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246789.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032409.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAS1	NM_016816.4	MANE Select	c.*84G>A		3_prime_UTR	Exon 6 of 6	NP_058132.2	P00973-1
OAS1	NM_001032409.3		c.1189G>A	p.Gly397Arg	missense	Exon 6 of 6	NP_001027581.1	P00973-3
OAS1	NM_001406020.1		c.1165G>A	p.Gly389Arg	missense	Exon 6 of 6	NP_001392949.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000445409.7	TSL:1	c.1189G>A	p.Gly397Arg	missense	Exon 6 of 6	ENSP00000388001.2	P00973-3
OAS1	ENST00000202917.10	TSL:1 MANE Select	c.*84G>A		3_prime_UTR	Exon 6 of 6	ENSP00000202917.5	P00973-1
OAS1	ENST00000452357.7	TSL:1	c.*1880G>A		3_prime_UTR	Exon 5 of 5	ENSP00000415721.2	P00973-2

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

113947

AN:

151954

Hom.:

43901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.705

GnomAD2 exomes

AF:

0.715

AC:

168981

AN:

236406

AF XY:

0.705

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.505

Gnomad EAS exome

AF:

0.786

Gnomad FIN exome

AF:

0.737

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.669

AC:

973286

AN:

1455378

Hom.:

328925

Cov.:

AF XY:

0.668

AC XY:

483098

AN XY:

723296

show subpopulations

African (AFR)

AF:

0.941

AC:

31387

AN:

33356

American (AMR)

AF:

0.819

AC:

35683

AN:

43560

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

13244

AN:

25890

East Asian (EAS)

AF:

0.796

AC:

31412

AN:

39472

South Asian (SAS)

AF:

0.692

AC:

59212

AN:

85524

European-Finnish (FIN)

AF:

0.730

AC:

38727

AN:

53068

Middle Eastern (MID)

AF:

0.581

AC:

3346

AN:

5760

European-Non Finnish (NFE)

AF:

0.650

AC:

720303

AN:

1108620

Other (OTH)

AF:

0.665

AC:

39972

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19086

38171

57257

76342

95428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18994

37988

56982

75976

94970

<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:

114077

AN:

152072

Hom.:

43967

Cov.:

AF XY:

0.753

AC XY:

55945

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.930

AC:

38600

AN:

41508

American (AMR)

AF:

0.767

AC:

11729

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1737

AN:

3470

East Asian (EAS)

AF:

0.774

AC:

3982

AN:

5144

South Asian (SAS)

AF:

0.709

AC:

3405

AN:

4800

European-Finnish (FIN)

AF:

0.729

AC:

7707

AN:

10576

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.657

AC:

44625

AN:

67966

Other (OTH)

AF:

0.708

AC:

1498

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1299

2597

3896

5194

6493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.677

Hom.:

148881

Bravo

AF:

0.763

TwinsUK

AF:

0.645

AC:

2391

ALSPAC

AF:

0.660

AC:

2545

ESP6500AA

AF:

0.923

AC:

4067

ESP6500EA

AF:

0.646

AC:

5555

ExAC

AF:

0.709

AC:

85510

Asia WGS

AF:

0.767

AC:

2666

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

OAS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

(source)

DANN

Benign

0.51

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.32

MetaRNN

Benign

9.1e-7

MetaSVM

Benign

-1.0

PhyloP100

-0.75

PROVEAN

Benign

0.25

REVEL

Benign

0.052

Sift

Benign

0.85

Polyphen

0.075

Vest4

0.043

MutPred

0.29

Gain of sheet (P = 0.0125)

MPC

0.075

ClinPred

0.00056

GERP RS

0.60

gMVP

0.088

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over