dbSNP rs7135579: OAS1:c.1168-2801C>T (chr12-112929077-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 ENST00000540589.3(OAS1):c.1168-2801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 152,298 control chromosomes in the GnomAD database, including 461 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 0.066 ( 461 hom., cov: 33)

Consequence

OAS1
ENST00000540589.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

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:

Genome browser will be placed here

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=-0.69).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
OAS1	NM_001320151.2 link	c.1039-2801C>T	intron_variant	Intron 5 of 5	NP_001307080.1
OAS1	NM_001406025.1 link	c.1015-2801C>T	intron_variant	Intron 5 of 5	NP_001392954.1
OAS1	NR_175991.1 link	n.1344-2801C>T	intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
OAS1	ENST00000540589.3 link	c.1168-2801C>T	intron_variant	Intron 6 of 6	1	ENSP00000474083.2
OAS1	ENST00000552526.2 link	c.1083-2801C>T	intron_variant	Intron 6 of 6	1	ENSP00000475139.2
OAS1	ENST00000551241.6 link	c.1039-2801C>T	intron_variant	Intron 5 of 5	1	ENSP00000448790.1
ENSG00000257452	ENST00000552784.1 link	n.354-20399G>A	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10075

AN:

152180

Hom.:

463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0601

Gnomad ASJ

AF:

0.0617

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0674

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

GnomAD4 genome

AF:

0.0661

AC:

10067

AN:

152298

Hom.:

461

Cov.:

AF XY:

0.0611

AC XY:

4548

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0178

AC:

740

AN:

41560

American (AMR)

AF:

0.0599

AC:

917

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0617

AC:

214

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0108

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0587

AC:

623

AN:

10622

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.107

AC:

7246

AN:

68014

Other (OTH)

AF:

0.0662

AC:

140

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

489

978

1468

1957

2446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0847

Hom.:

445

Bravo

AF:

0.0649

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.5

(source)

DANN

Benign

0.85

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