rs1131454

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016816.4(OAS1):c.484G>A(p.Gly162Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,612,274 control chromosomes in the GnomAD database, including 259,474 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20096 hom., cov: 30)

Exomes 𝑓: 0.57 ( 239378 hom. )

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.0220

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 links:

OAS1 (HGNC:):

OAS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1463453E-5).

BP6

Variant 12-112911065-G-A is Benign according to our data. Variant chr12-112911065-G-A is described in ClinVar as [Benign]. Clinvar id is 13985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS1	NM_016816.4 linkuse as main transcript	c.484G>A	p.Gly162Ser	missense_variant	3/6	ENST00000202917.10	NP_058132.2	P00973-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10 linkuse as main transcript	c.484G>A	p.Gly162Ser	missense_variant	3/6	1	NM_016816.4	ENSP00000202917.5		P00973-1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73719

AN:

151706

Hom.:

20085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.498

GnomAD3 exomes

AF:

0.569

AC:

142536

AN:

250300

Hom.:

42483

AF XY:

0.571

AC XY:

77277

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.699

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.618

Gnomad SAS exome

AF:

0.570

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.579

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.567

AC:

828699

AN:

1460450

Hom.:

239378

Cov.:

AF XY:

0.568

AC XY:

412896

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.690

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.573

Gnomad4 FIN exome

AF:

0.624

Gnomad4 NFE exome

AF:

0.575

Gnomad4 OTH exome

AF:

0.532

GnomAD4 genome

AF:

0.486

AC:

73751

AN:

151824

Hom.:

20096

Cov.:

AF XY:

0.494

AC XY:

36626

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.609

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.610

Gnomad4 SAS

AF:

0.579

Gnomad4 FIN

AF:

0.628

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.553

Hom.:

41451

Bravo

AF:

0.472

TwinsUK

AF:

0.581

AC:

2153

ALSPAC

AF:

0.588

AC:

2267

ESP6500AA

AF:

0.245

AC:

1081

ESP6500EA

AF:

0.566

AC:

4868

ExAC

AF:

0.562

AC:

68241

Asia WGS

AF:

0.563

AC:

1954

AN:

3478

EpiCase

AF:

0.556

EpiControl

AF:

0.560

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 16014697) -

OAS1 polymorphism

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Feb 01, 2006

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 87% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

OAS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.025

DANN

Benign

0.69

DEOGEN2

Benign

0.047

T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.061

T;T;T;T;T

MetaRNN

Benign

0.000011

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L;L;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.34

T;T;T;T;T

Sift4G

Benign

0.68

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.048

MPC

0.070

ClinPred

0.0081

GERP RS

-5.9

Varity_R

0.082

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over