OAS1 p.Gly397Arg

Variant names:

• chr12-112919637-G-C
• ENST00000445409.7:c.1189G>C
• OAS1 p.Gly397Arg

Your query was ambiguous. Multiple possible variants found:

• chr12-112919637-G-C
• chr12-112919637-G-A
• chr12-112919637-GGA-CGT
• chr12-112919637-GGA-CGC
• chr12-112919637-GGA-CGG
• chr12-112919637-GGA-AGG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001032409.3(OAS1):​c.1189G>C​(p.Gly397Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OAS1 NM_001032409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• pulmonary alveolar proteinosis with hypogammaglobulinemia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000257452 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037021607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032409.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	NM_016816.4	MANE Select	c.*84G>C		3_prime_UTR	Exon 6 of 6	NP_058132.2	P00973-1
	OAS1	NM_001032409.3		c.1189G>C	p.Gly397Arg	missense	Exon 6 of 6	NP_001027581.1	P00973-3
	OAS1	NM_001406020.1		c.1165G>C	p.Gly389Arg	missense	Exon 6 of 6	NP_001392949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000445409.7	TSL:1	c.1189G>C	p.Gly397Arg	missense	Exon 6 of 6	ENSP00000388001.2	P00973-3
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.*84G>C		3_prime_UTR	Exon 6 of 6	ENSP00000202917.5	P00973-1
	OAS1	ENST00000452357.7	TSL:1	c.*1880G>C		3_prime_UTR	Exon 5 of 5	ENSP00000415721.2	P00973-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.87e-7 AC: 1 AN: 1455522 Hom.: 0 Cov.: 67 AF XY: 0.00 AC XY: 0 AN XY: 723392

African (AFR) AF: 0.00 AC: 0 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 43568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25890

East Asian (EAS) AF: 0.00 AC: 0 AN: 39474

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108728

Other (OTH) AF: 0.00 AC: 0 AN: 60132

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.66
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.00062	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.75
PROVEAN	Benign	0.25	N
REVEL	Benign	0.052
Sift	Benign	0.85	T
gMVP		0.088
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-113357442;