rs10774671

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1039-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,598,136 control chromosomes in the GnomAD database, including 340,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28580 hom., cov: 32)

Exomes 𝑓: 0.65 ( 311607 hom. )

Consequence

OAS1
NM_016816.4 splice_acceptor, intron

Scores

Splicing: ADA: 0.0007956

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.729

Publications

217 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 (BayesDel_addAF=-0.802932).

BP6

Variant 12-112919388-G-A is Benign according to our data. Variant chr12-112919388-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1156518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016816.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	NM_016816.4	MANE Select	c.1039-1G>A	splice_acceptor intron	N/A	NP_058132.2	P00973-1
OAS1	NM_001406022.1		c.*675G>A	3_prime_UTR	Exon 6 of 6	NP_001392951.1	H0YIB8
OAS1	NM_001406023.1		c.*675G>A	3_prime_UTR	Exon 6 of 6	NP_001392952.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000452357.7	TSL:1	c.*1631G>A	3_prime_UTR	Exon 5 of 5	ENSP00000415721.2	P00973-2
OAS1	ENST00000202917.10	TSL:1 MANE Select	c.1039-1G>A	splice_acceptor intron	N/A	ENSP00000202917.5	P00973-1
OAS1	ENST00000445409.7	TSL:1	c.1039-99G>A	intron	N/A	ENSP00000388001.2	P00973-3

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91290

AN:

151964

Hom.:

28562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.704

Gnomad FIN

AF:

0.728

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.592

GnomAD2 exomes

AF:

0.672

AC:

166967

AN:

248584

AF XY:

0.672

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.787

Gnomad FIN exome

AF:

0.738

Gnomad NFE exome

AF:

0.655

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.651

AC:

941833

AN:

1446056

Hom.:

311607

Cov.:

AF XY:

0.652

AC XY:

469297

AN XY:

719562

show subpopulations

African (AFR)

AF:

0.401

AC:

13367

AN:

33342

American (AMR)

AF:

0.783

AC:

34920

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

11927

AN:

25866

East Asian (EAS)

AF:

0.796

AC:

31529

AN:

39604

South Asian (SAS)

AF:

0.690

AC:

59067

AN:

85612

European-Finnish (FIN)

AF:

0.730

AC:

38908

AN:

53310

Middle Eastern (MID)

AF:

0.515

AC:

2954

AN:

5740

European-Non Finnish (NFE)

AF:

0.648

AC:

711925

AN:

1098120

Other (OTH)

AF:

0.622

AC:

37236

AN:

59862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

14291

28582

42874

57165

71456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18548

37096

55644

74192

92740

<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:

0.601

AC:

91352

AN:

152080

Hom.:

28580

Cov.:

AF XY:

0.609

AC XY:

45280

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.422

AC:

17510

AN:

41460

American (AMR)

AF:

0.702

AC:

10729

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

1587

AN:

3472

East Asian (EAS)

AF:

0.773

AC:

3992

AN:

5164

South Asian (SAS)

AF:

0.705

AC:

3400

AN:

4824

European-Finnish (FIN)

AF:

0.728

AC:

7702

AN:

10574

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.653

AC:

44412

AN:

67998

Other (OTH)

AF:

0.591

AC:

1245

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1789

3577

5366

7154

8943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.625

Hom.:

90882

Bravo

AF:

0.592

TwinsUK

AF:

0.642

AC:

2381

ALSPAC

AF:

0.658

AC:

2536

ESP6500AA

AF:

0.435

AC:

1917

ESP6500EA

AF:

0.638

AC:

5490

ExAC

AF:

0.665

AC:

80727

Asia WGS

AF:

0.699

AC:

2431

AN:

3478

EpiCase

AF:

0.632

EpiControl

AF:

0.638

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

OAS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.87

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.056

PhyloP100

0.73

GERP RS

2.9

Mutation Taster

=70/30

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00080

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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