Genetic Variant OAS1:c.1168-949G>A (chr12-112930929-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000540589.3(OAS1):c.1168-949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,168 control chromosomes in the GnomAD database, including 541 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 0.065 ( 541 hom., cov: 33)

Consequence

OAS1
ENST00000540589.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.259

Publications

6 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
OAS1	NM_001320151.2 link	c.1039-949G>A	intron_variant	Intron 5 of 5	NP_001307080.1	P00973-4
OAS1	NM_001406025.1 link	c.1015-949G>A	intron_variant	Intron 5 of 5	NP_001392954.1
OAS1	NR_175991.1 link	n.1344-949G>A	intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
OAS1	ENST00000540589.3 link	c.1168-949G>A	intron_variant	Intron 6 of 6	1	ENSP00000474083.2	S4R3A5
OAS1	ENST00000552526.2 link	c.1083-949G>A	intron_variant	Intron 6 of 6	1	ENSP00000475139.2	S4R467
OAS1	ENST00000551241.6 link	c.1039-949G>A	intron_variant	Intron 5 of 5	1	ENSP00000448790.1	P00973-4
ENSG00000257452	ENST00000552784.1 link	n.354-22251C>T	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9906

AN:

152050

Hom.:

541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.0590

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0646

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

GnomAD4 genome

AF:

0.0652

AC:

9915

AN:

152168

Hom.:

541

Cov.:

AF XY:

0.0714

AC XY:

5309

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0325

AC:

1351

AN:

41528

American (AMR)

AF:

0.0923

AC:

1411

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

205

AN:

3472

East Asian (EAS)

AF:

0.313

AC:

1610

AN:

5150

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4824

European-Finnish (FIN)

AF:

0.114

AC:

1205

AN:

10592

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0499

AC:

3390

AN:

68000

Other (OTH)

AF:

0.0644

AC:

136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

462

925

1387

1850

2312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0545

Hom.:

558

Bravo

AF:

0.0647

Asia WGS

AF:

0.148

AC:

515

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.0

(source)

DANN

Benign

0.33

PhyloP100

-0.26

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over