dbSNP rs12298890: OAS1:c.884+278C>T (chr12-112917016-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016816.4(OAS1):c.884+278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 421,622 control chromosomes in the GnomAD database, including 1 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 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

OAS1
NM_016816.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.374

Publications

0 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS2

High AC in GnomAd4 at 201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_016816.4 link	c.884+278C>T		intron_variant	Intron 4 of 5	ENST00000202917.10	NP_058132.2	P00973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10 link	c.884+278C>T		intron_variant	Intron 4 of 5	1	NM_016816.4	ENSP00000202917.5		P00973-1

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD4 exome

AF:

0.000215

AC:

AN:

269380

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

140124

show subpopulations

African (AFR)

AF:

0.00503

AC:

AN:

9142

American (AMR)

AF:

0.000337

AC:

AN:

11872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8704

East Asian (EAS)

AF:

0.00

AC:

AN:

18152

South Asian (SAS)

AF:

0.00

AC:

AN:

27790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14608

Middle Eastern (MID)

AF:

0.000828

AC:

AN:

1208

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

161876

Other (OTH)

AF:

0.000250

AC:

AN:

16028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00132

AC:

201

AN:

152242

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00443

AC:

184

AN:

41538

American (AMR)

AF:

0.000981

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00160

Hom.:

Bravo

AF:

0.00152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.53

PhyloP100

-0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over