12-112907117-C-T

Variant names:

• chr12-112907117-C-T
• rs2043305566
• NM_016816.4:c.78C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_016816.4(OAS1):​c.78C>T​(p.Phe26Phe) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OAS1 NM_016816.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.442
• Publications: 0 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)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-112907117-C-T is Benign according to our data. Variant chr12-112907117-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1626456.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.442 with no splicing effect.

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.78C>T	p.Phe26Phe	synonymous	Exon 1 of 6	NP_058132.2	P00973-1
	OAS1	NM_001032409.3		c.78C>T	p.Phe26Phe	synonymous	Exon 1 of 6	NP_001027581.1	P00973-3
	OAS1	NM_001406020.1		c.78C>T	p.Phe26Phe	synonymous	Exon 1 of 6	NP_001392949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS1	ENST00000202917.10	TSL:1 MANE Select	c.78C>T	p.Phe26Phe	synonymous	Exon 1 of 6	ENSP00000202917.5	P00973-1
	OAS1	ENST00000445409.7	TSL:1	c.78C>T	p.Phe26Phe	synonymous	Exon 1 of 6	ENSP00000388001.2	P00973-3
	OAS1	ENST00000540589.3	TSL:1	c.78C>T	p.Phe26Phe	synonymous	Exon 1 of 7	ENSP00000474083.2	S4R3A5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.80
PhyloP100		0.44
PromoterAI		-0.074	Neutral

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: rs2043305566; hg19: chr12-113344922;