chr12-112929538-A-G

Variant names:

• chr12-112929538-A-G
• rs2384071
• ENST00000540589.3:c.1168-2340A>G

Variant summary

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

The ENST00000540589.3(OAS1):​c.1168-2340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,132 control chromosomes in the GnomAD database, including 43,373 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 0.74 (43373 hom., cov: 32)
• Consequence: OAS1 ENST00000540589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 12 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540589.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	NM_001320151.2		c.1039-2340A>G		intron	N/A	NP_001307080.1
	OAS1	NM_001406025.1		c.1015-2340A>G		intron	N/A	NP_001392954.1
	OAS1	NR_175991.1		n.1344-2340A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000540589.3	TSL:1	c.1168-2340A>G		intron	N/A	ENSP00000474083.2
	OAS1	ENST00000552526.2	TSL:1	c.1083-2340A>G		intron	N/A	ENSP00000475139.2
	OAS1	ENST00000551241.6	TSL:1	c.1039-2340A>G		intron	N/A	ENSP00000448790.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113016 AN: 152014 Hom.: 43306 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.744 AC: 113148 AN: 152132 Hom.: 43373 Cov.: 32 AF XY: 0.747 AC XY: 55526 AN XY: 74368

African (AFR) AF: 0.935 AC: 38830 AN: 41508

American (AMR) AF: 0.752 AC: 11507 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1732 AN: 3468

East Asian (EAS) AF: 0.775 AC: 4009 AN: 5172

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

European-Finnish (FIN) AF: 0.727 AC: 7690 AN: 10576

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43768 AN: 67986

Other (OTH) AF: 0.694 AC: 1464 AN: 2108

Alfa AF: 0.709 Hom.: 4789

Bravo AF: 0.755

Asia WGS AF: 0.770 AC: 2679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2384071; hg19: chr12-113367343;