dbSNP rs7967461: OAS1:c.*32G>C (chr12-112931954-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001320151.2(OAS1):c.*32G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 700,014 control chromosomes in the GnomAD database, including 170,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 43022 hom., cov: 32)

Exomes 𝑓: 0.68 ( 127177 hom. )

Consequence

OAS1
NM_001320151.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.365

Publications

22 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.009).

BP6

Variant 12-112931954-G-C is Benign according to our data. Variant chr12-112931954-G-C is described in ClinVar as Benign. ClinVar VariationId is 2687938.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320151.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	NM_001320151.2	c.*32G>C	3_prime_UTR	Exon 6 of 6	NP_001307080.1	P00973-4
OAS1	NM_001406025.1	c.*32G>C	3_prime_UTR	Exon 6 of 6	NP_001392954.1
OAS1	NR_175991.1	n.1420G>C	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000540589.3	TSL:1	c.*32G>C	3_prime_UTR	Exon 7 of 7	ENSP00000474083.2	S4R3A5
OAS1	ENST00000552526.2	TSL:1	c.*73G>C	3_prime_UTR	Exon 7 of 7	ENSP00000475139.2	S4R467
OAS1	ENST00000551241.6	TSL:1	c.*32G>C	3_prime_UTR	Exon 6 of 6	ENSP00000448790.1	P00973-4

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112619

AN:

151962

Hom.:

42963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.691

GnomAD2 exomes

AF:

0.698

AC:

94770

AN:

135748

AF XY:

0.690

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.808

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.675

AC:

369964

AN:

547934

Hom.:

127177

Cov.:

AF XY:

0.672

AC XY:

199397

AN XY:

296684

show subpopulations

African (AFR)

AF:

0.923

AC:

14385

AN:

15580

American (AMR)

AF:

0.802

AC:

27655

AN:

34476

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

10120

AN:

19902

East Asian (EAS)

AF:

0.801

AC:

25632

AN:

31988

South Asian (SAS)

AF:

0.692

AC:

43074

AN:

62216

European-Finnish (FIN)

AF:

0.725

AC:

24306

AN:

33536

Middle Eastern (MID)

AF:

0.583

AC:

2335

AN:

4002

European-Non Finnish (NFE)

AF:

0.640

AC:

202046

AN:

315758

Other (OTH)

AF:

0.670

AC:

20411

AN:

30476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

5601

11203

16804

22406

28007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

950

1900

2850

3800

4750

<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:

0.741

AC:

112741

AN:

152080

Hom.:

43022

Cov.:

AF XY:

0.745

AC XY:

55337

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.927

AC:

38483

AN:

41510

American (AMR)

AF:

0.750

AC:

11458

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1731

AN:

3462

East Asian (EAS)

AF:

0.776

AC:

4018

AN:

5180

South Asian (SAS)

AF:

0.709

AC:

3415

AN:

4820

European-Finnish (FIN)

AF:

0.727

AC:

7672

AN:

10548

Middle Eastern (MID)

AF:

0.592

AC:

173

AN:

292

European-Non Finnish (NFE)

AF:

0.644

AC:

43762

AN:

67972

Other (OTH)

AF:

0.694

AC:

1464

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1412

2824

4237

5649

7061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.581

Hom.:

2810

Bravo

AF:

0.753

Asia WGS

AF:

0.768

AC:

2671

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.1

(source)

DANN

Benign

0.71

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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