12-112912991-G-T

Variant names:

• chr12-112912991-G-T
• rs2057778
• NM_016816.4:c.654+1756G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016816.4(OAS1):​c.654+1756G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,166 control chromosomes in the GnomAD database, including 44,319 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (44319 hom., cov: 32)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 25 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS1	NM_016816.4	c.654+1756G>T		intron_variant	Intron 3 of 5	ENST00000202917.10	NP_058132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS1	ENST00000202917.10	c.654+1756G>T		intron_variant	Intron 3 of 5	1	NM_016816.4	ENSP00000202917.5

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114375 AN: 152048 Hom.: 44250 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.704

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.753 AC: 114509 AN: 152166 Hom.: 44319 Cov.: 32 AF XY: 0.755 AC XY: 56145 AN XY: 74388

African (AFR) AF: 0.938 AC: 38986 AN: 41564

American (AMR) AF: 0.767 AC: 11725 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1738 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4003 AN: 5168

South Asian (SAS) AF: 0.708 AC: 3416 AN: 4822

European-Finnish (FIN) AF: 0.729 AC: 7701 AN: 10568

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.657 AC: 44649 AN: 67970

Other (OTH) AF: 0.707 AC: 1496 AN: 2116

Alfa AF: 0.734 Hom.: 6810

Bravo AF: 0.765

Asia WGS AF: 0.768 AC: 2670 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.42
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2057778; hg19: chr12-113350796;