chr12-112913715-T-G

Variant names:

• chr12-112913715-T-G
• rs2285934
• NM_016816.4:c.654+2480T>G

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+2480T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,980 control chromosomes in the GnomAD database, including 30,948 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 0.63 (30948 hom., cov: 32)
• Consequence: OAS1 NM_016816.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 27 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	NM_016816.4	MANE Select	c.654+2480T>G		intron	N/A	NP_058132.2
	OAS1	NM_001032409.3		c.654+2480T>G		intron	N/A	NP_001027581.1
	OAS1	NM_001406020.1		c.630+2457T>G		intron	N/A	NP_001392949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.654+2480T>G		intron	N/A	ENSP00000202917.5
	OAS1	ENST00000445409.7	TSL:1	c.654+2480T>G		intron	N/A	ENSP00000388001.2
	OAS1	ENST00000540589.3	TSL:1	c.654+2480T>G		intron	N/A	ENSP00000474083.2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95916 AN: 151862 Hom.: 30913 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.632 AC: 96012 AN: 151980 Hom.: 30948 Cov.: 32 AF XY: 0.639 AC XY: 47466 AN XY: 74324

African (AFR) AF: 0.516 AC: 21375 AN: 41440

American (AMR) AF: 0.717 AC: 10961 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1736 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4017 AN: 5172

South Asian (SAS) AF: 0.707 AC: 3406 AN: 4818

European-Finnish (FIN) AF: 0.728 AC: 7645 AN: 10500

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44760 AN: 67974

Other (OTH) AF: 0.626 AC: 1324 AN: 2116

Alfa AF: 0.649 Hom.: 4873

Bravo AF: 0.627

Asia WGS AF: 0.716 AC: 2482 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		0.080
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: rs2285934; hg19: chr12-113351520;