rs2660

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001032409.3(OAS1):c.1189G>A(p.Gly397Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,607,450 control chromosomes in the GnomAD database, including 372,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43967 hom., cov: 30)

Exomes 𝑓: 0.67 ( 328925 hom. )

Consequence

OAS1
NM_001032409.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.747

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:

ENSG00000257452 (HGNC:):

ENSG00000257452 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a lipid_moiety_binding_region S-geranylgeranyl cysteine (size 0) in uniprot entity OAS1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=9.122781E-7).

BP6

Variant 12-112919637-G-A is Benign according to our data. Variant chr12-112919637-G-A is described in ClinVar as [Benign]. Clinvar id is 1246789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_016816.4 link	c.*84G>A		3_prime_UTR_variant	Exon 6 of 6	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.*84G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_016816.4	ENSP00000202917.5		P00973-1

Frequencies

GnomAD3 genomes

AF:

0.750

AC:

113947

AN:

151954

Hom.:

43901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.705

GnomAD3 exomes

AF:

0.715

AC:

168981

AN:

236406

Hom.:

61483

AF XY:

0.705

AC XY:

89845

AN XY:

127530

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.505

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.693

Gnomad FIN exome

AF:

0.737

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.671

GnomAD4 exome

AF:

0.669

AC:

973286

AN:

1455378

Hom.:

328925

Cov.:

AF XY:

0.668

AC XY:

483098

AN XY:

723296

show subpopulations

Gnomad4 AFR exome

AF:

0.941

Gnomad4 AMR exome

AF:

0.819

Gnomad4 ASJ exome

AF:

0.512

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.650

Gnomad4 OTH exome

AF:

0.665

GnomAD4 genome

AF:

0.750

AC:

114077

AN:

152072

Hom.:

43967

Cov.:

AF XY:

0.753

AC XY:

55945

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.930

Gnomad4 AMR

AF:

0.767

Gnomad4 ASJ

AF:

0.501

Gnomad4 EAS

AF:

0.774

Gnomad4 SAS

AF:

0.709

Gnomad4 FIN

AF:

0.729

Gnomad4 NFE

AF:

0.657

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.664

Hom.:

72804

Bravo

AF:

0.763

TwinsUK

AF:

0.645

AC:

2391

ALSPAC

AF:

0.660

AC:

2545

ESP6500AA

AF:

0.923

AC:

4067

ESP6500EA

AF:

0.646

AC:

5555

ExAC

AF:

0.709

AC:

85510

Asia WGS

AF:

0.767

AC:

2666

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21638280) -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 89. Only high quality variants are reported. -

OAS1-related disorder

Benign:1

May 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

DANN

Benign

0.51

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.32

MetaRNN

Benign

9.1e-7

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.25

REVEL

Benign

0.052

Sift

Benign

0.85

Polyphen

0.075

Vest4

0.043

MutPred

0.29

Gain of sheet (P = 0.0125);

MPC

0.075

ClinPred

0.00056

GERP RS

0.60

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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