12-112907078-C-CCCA

Variant names:

• chr12-112907078-C-CCCA
• rs2136290657
• NM_016816.4:c.39_40insCCA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PM4_Supporting BP6_Moderate

The NM_016816.4(OAS1):​c.39_40insCCA​(p.Asp13_Lys14insPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OAS1 NM_016816.4 conservative_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016816.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 12-112907078-C-CCCA is Benign according to our data. Variant chr12-112907078-C-CCCA is described in ClinVar as Likely_benign. ClinVar VariationId is 1348204.Status of the report is criteria_provided_single_submitter, 1 stars.

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.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	Exon 1 of 6	NP_058132.2	P00973-1
	OAS1	NM_001032409.3		c.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	Exon 1 of 6	NP_001027581.1	P00973-3
	OAS1	NM_001406020.1		c.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	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.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	Exon 1 of 6	ENSP00000202917.5	P00973-1
	OAS1	ENST00000445409.7	TSL:1	c.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	Exon 1 of 6	ENSP00000388001.2	P00973-3
	OAS1	ENST00000540589.3	TSL:1	c.39_40insCCA	p.Asp13_Lys14insPro	conservative_inframe_insertion	Exon 1 of 7	ENSP00000474083.2	S4R3A5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs2136290657; hg19: chr12-113344883;