chr12-112913715-T-C

Variant names:

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

Variant summary

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

The NM_016816.4(OAS1):​c.654+2480T>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (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: 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 (BayesDel_noAF=-0.89).

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>C		intron	N/A	NP_058132.2
	OAS1	NM_001032409.3		c.654+2480T>C		intron	N/A	NP_001027581.1
	OAS1	NM_001406020.1		c.630+2457T>C		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>C		intron	N/A	ENSP00000202917.5
	OAS1	ENST00000445409.7	TSL:1	c.654+2480T>C		intron	N/A	ENSP00000388001.2
	OAS1	ENST00000540589.3	TSL:1	c.654+2480T>C		intron	N/A	ENSP00000474083.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.78
PhyloP100		0.080

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;