Variant chr12-112919432-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/18 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 Likely 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1567193.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 176 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_016816.4 link	c.1082G>T	p.Arg361Met	missense_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.1082G>T	p.Arg361Met	missense_variant	Exon 6 of 6	1	NM_016816.4	ENSP00000202917.5		P00973-1

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

GnomAD3 exomes

AF:

0.00148

AC:

371

AN:

250988

Hom.:

AF XY:

0.00128

AC XY:

174

AN XY:

135638

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 SAS exome

AF:

0.000196

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

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152220

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000110

Hom.:

17453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000939

AC:

114

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.7

DANN

Benign

0.54

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.26

T;.

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

0.040

N;.

REVEL

Benign

0.0

Sift

Benign

0.10

T;.

Sift4G

Benign

0.33

T;.

Polyphen

0.0

B;.

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

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

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