12-112919432-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016816.4(OAS1):c.1082G>T(p.Arg361Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,613,902 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R361T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 9 hom. )

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.37

Publications

54 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035489202).

BP6

Variant 12-112919432-G-T is Benign according to our data. Variant chr12-112919432-G-T is described in ClinVar as Benign. ClinVar VariationId is 1567193.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 176 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016816.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAS1	NM_016816.4	MANE Select	c.1082G>T	p.Arg361Met	missense	Exon 6 of 6	NP_058132.2	P00973-1
OAS1	NM_001406021.1		c.1058G>T	p.Arg353Met	missense	Exon 6 of 6	NP_001392950.1	A0A7P0Z4N8
OAS1	NM_001406027.1		c.608G>T	p.Arg203Met	missense	Exon 4 of 4	NP_001392956.1	A0A7P0T8F9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAS1	ENST00000202917.10	TSL:1 MANE Select	c.1082G>T	p.Arg361Met	missense	Exon 6 of 6	ENSP00000202917.5	P00973-1
OAS1	ENST00000552526.2	TSL:1	c.1082G>T	p.Arg361Met	missense splice_region	Exon 6 of 7	ENSP00000475139.2	S4R467
OAS1	ENST00000452357.7	TSL:1	c.*1675G>T		3_prime_UTR	Exon 5 of 5	ENSP00000415721.2	P00973-2

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00148

AC:

371

AN:

250988

AF XY:

0.00128

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000592

AC:

866

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

402

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0130

AC:

692

AN:

53414

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000129

AC:

143

AN:

1111836

Other (OTH)

AF:

0.000298

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

144

192

240

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:

0.00116

AC:

176

AN:

152220

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0155

AC:

164

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000110

Hom.:

17453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000939

AC:

114

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.7

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.010

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

-2.4

PrimateAI

Benign

0.25

PROVEAN

Benign

0.040

REVEL

Benign

0.0

Sift

Benign

0.10

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.088

MutPred

0.30

Loss of catalytic residue at R361 (P = 0.0497)

MVP

0.081

ClinPred

0.015

GERP RS

-4.5

Varity_R

0.030

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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