rs1051042

Variant names:

• chr12-112919432-G-C
• rs1051042
• NM_016816.4:c.1082G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-112919432-G-C
• chr12-112919432-G-T
• chr12-112919432-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 15/20 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. R361M) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.75 (43887 hom., cov: 33)
  • Exomes 𝑓: 0.67 (330073 hom.)
• Consequence: OAS1 NM_016816.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.37
• Publications: 54 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016816.4. 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.1082G>C	p.Arg361Thr	missense	Exon 6 of 6	NP_058132.2	P00973-1
	OAS1	NM_001406021.1		c.1058G>C	p.Arg353Thr	missense	Exon 6 of 6	NP_001392950.1	A0A7P0Z4N8
	OAS1	NM_001406027.1		c.608G>C	p.Arg203Thr	missense	Exon 4 of 4	NP_001392956.1	A0A7P0T8F9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.1082G>C	p.Arg361Thr	missense	Exon 6 of 6	ENSP00000202917.5	P00973-1
	OAS1	ENST00000552526.2	TSL:1	c.1082G>C	p.Arg361Thr	missense splice_region	Exon 6 of 7	ENSP00000475139.2	S4R467
	OAS1	ENST00000452357.7	TSL:1	c.*1675G>C		3_prime_UTR	Exon 5 of 5	ENSP00000415721.2	P00973-2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113856 AN: 152050 Hom.: 43821 Cov.: 33

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

GnomAD2 exomes AF: 0.713 AC: 178945 AN: 250988 AF XY: 0.703

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 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.: 50 AF XY: 0.668 AC XY: 484525 AN XY: 725396

African (AFR) AF: 0.941 AC: 31499 AN: 33476

American (AMR) AF: 0.819 AC: 36649 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 13367 AN: 26118

East Asian (EAS) AF: 0.796 AC: 31592 AN: 39690

South Asian (SAS) AF: 0.692 AC: 59647 AN: 86148

European-Finnish (FIN) AF: 0.717 AC: 38279 AN: 53404

Middle Eastern (MID) AF: 0.581 AC: 3348 AN: 5766

European-Non Finnish (NFE) AF: 0.650 AC: 720524 AN: 1108166

Other (OTH) AF: 0.665 AC: 40063 AN: 60250

GnomAD4 genome AF: 0.749 AC: 113986 AN: 152168 Hom.: 43887 Cov.: 33 AF XY: 0.751 AC XY: 55855 AN XY: 74392

African (AFR) AF: 0.930 AC: 38641 AN: 41550

American (AMR) AF: 0.767 AC: 11737 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1737 AN: 3472

East Asian (EAS) AF: 0.773 AC: 3992 AN: 5166

South Asian (SAS) AF: 0.708 AC: 3413 AN: 4818

European-Finnish (FIN) AF: 0.713 AC: 7531 AN: 10560

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44645 AN: 67992

Other (OTH) AF: 0.708 AC: 1496 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	OAS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.49
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.4
PrimateAI	Benign	0.29	T
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	T
GERP RS		-4.5
Varity_R		0.031
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051042; hg19: chr12-113357237; COSMIC: COSV52537714; COSMIC: COSV52537714;