Genetic Variant OAS1:c.1168-2374C>T (chr12-112929504-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001320151.2(OAS1):c.1039-2374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,164 control chromosomes in the GnomAD database, including 43,390 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 43390 hom., cov: 32)

Consequence

OAS1
NM_001320151.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Publications

16 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 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.1039-2374C>T	intron	N/A	NP_001307080.1	P00973-4
OAS1	NM_001406025.1	c.1015-2374C>T	intron	N/A	NP_001392954.1
OAS1	NR_175991.1	n.1344-2374C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000540589.3	TSL:1	c.1168-2374C>T	intron	N/A	ENSP00000474083.2	S4R3A5
OAS1	ENST00000552526.2	TSL:1	c.1083-2374C>T	intron	N/A	ENSP00000475139.2	S4R467
OAS1	ENST00000551241.6	TSL:1	c.1039-2374C>T	intron	N/A	ENSP00000448790.1	P00973-4

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113053

AN:

152046

Hom.:

43326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.935

Gnomad AMI

AF:

0.617

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.691

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.744

AC:

113181

AN:

152164

Hom.:

43390

Cov.:

AF XY:

0.747

AC XY:

55531

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.935

AC:

38856

AN:

41540

American (AMR)

AF:

0.752

AC:

11502

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

1734

AN:

3472

East Asian (EAS)

AF:

0.775

AC:

4012

AN:

5176

South Asian (SAS)

AF:

0.708

AC:

3411

AN:

4816

European-Finnish (FIN)

AF:

0.727

AC:

7695

AN:

10578

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.644

AC:

43777

AN:

67988

Other (OTH)

AF:

0.694

AC:

1461

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1377

2754

4130

5507

6884

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:

0.717

Hom.:

6197

Bravo

AF:

0.755

Asia WGS

AF:

0.769

AC:

2675

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.6

(source)

DANN

Benign

0.23

PhyloP100

-0.79

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over