rs1131454

Positions:

• chr12-112911065-G-A
• chr12-112911065-G-C
• chr12-112911065-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: 0.0220

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]

(HGNC:):

ACMG classification

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	UniProt
OAS1	NM_016816.4	c.484G>A	p.Gly162Ser	missense_variant	3/6	ENST00000202917.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS1	ENST00000202917.10	c.484G>A	p.Gly162Ser	missense_variant	3/6	1	NM_016816.4	P2
	ENST00000552784.1	n.354-2387C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73719 AN: 151706 Hom.: 20085 Cov.: 30

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

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.: 43 AF XY: 0.568 AC XY: 412896 AN XY: 726498

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.: 30 AF XY: 0.494 AC XY: 36626 AN XY: 74184

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:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 16014697) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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, criteria provided, single submitter

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	T
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	N
LIST_S2	Benign	0.061	T;T;T;T;T
MetaRNN	Benign	0.000011	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;L;L;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs1131454; hg19: chr12-113348870; COSMIC: COSV52534422; COSMIC: COSV52534422;