12-112919432-G-C

Position:

chr12-112919432-G-C

Variant summary

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

The NM_016816.4(OAS1):c.1082G>C(p.Arg361Thr) 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 1,609,908 control chromosomes in the GnomAD database, including 373,960 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.75 ( 43887 hom., cov: 33)

Exomes 𝑓: 0.67 ( 330073 hom. )

Consequence

OAS1
NM_016816.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.37

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=1.1834173E-6).

BP6

Variant 12-112919432-G-C is Benign according to our data. Variant chr12-112919432-G-C is described in ClinVar as [Benign]. Clinvar id is 1168534.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/exons	MANE	Protein	UniProt
OAS1	NM_016816.4 linkuse as main transcript	c.1082G>C	p.Arg361Thr	missense_variant	6/6	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.1082G>C	p.Arg361Thr	missense_variant	6/6	1	NM_016816.4	ENSP00000202917.5		P00973-1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113856

AN:

152050

Hom.:

43821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.713

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.705

GnomAD3 exomes

AF:

0.713

AC:

178945

AN:

250988

Hom.:

65142

AF XY:

0.703

AC XY:

95325

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.787

Gnomad SAS exome

AF:

0.692

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.670

GnomAD4 exome

AF:

0.669

AC:

974968

AN:

1457740

Hom.:

330073

Cov.:

AF XY:

0.668

AC XY:

484525

AN XY:

725396

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:

0.717

Gnomad4 NFE exome

AF:

0.650

Gnomad4 OTH exome

AF:

0.665

GnomAD4 genome

AF:

0.749

AC:

113986

AN:

152168

Hom.:

43887

Cov.:

AF XY:

0.751

AC XY:

55855

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.930

Gnomad4 AMR

AF:

0.767

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.773

Gnomad4 SAS

AF:

0.708

Gnomad4 FIN

AF:

0.713

Gnomad4 NFE

AF:

0.657

Gnomad4 OTH

AF:

0.708

Alfa

AF:

0.643

Hom.:

17453

Bravo

AF:

0.763

TwinsUK

AF:

0.645

AC:

2390

ALSPAC

AF:

0.660

AC:

2544

ESP6500AA

AF:

0.923

AC:

4067

ESP6500EA

AF:

0.646

AC:

5554

ExAC

AF:

0.715

AC:

86858

Asia WGS

AF:

0.767

AC:

2666

AN:

3478

EpiCase

AF:

0.638

EpiControl

AF:

0.645

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

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 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

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

0.086

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

DANN

Benign

0.49

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.42

T;.

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.16

N;.

REVEL

Benign

0.0050

Sift

Benign

0.28

T;.

Sift4G

Benign

0.38

T;.

Polyphen

0.0

B;.

Vest4

0.026

ClinPred

0.0023

GERP RS

-4.5

Varity_R

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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