It happened around 5:30 a.m. near Front and Luzerne streets.
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According to SEPTA transit police, a man boarded the Route 57 bus and began arguing with the driver.
The suspect then threatened the driver, got off the bus and fired a shot from a handgun.
The bullet hit the windshield. SEPTA says no injuries were reported.
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The search continues for the suspect.
Anyone with information is asked to call SEPTA Transit Police at (215) 580-8111.