The fatal collision happened around 9:16 a.m. on the 6100 block of Harbinson Avenue.
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Investigators say a man, in his early 20s, driving a Mercedes westbound on Benner Street ran a red light.
The Mercedes was struck by a Ford E150 van traveling southbound on Harbison.
Chopper 6 over the scene showed both vehicles severely damaged, with the van ending up on its side on the sidewalk.
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The driver of the Mercedes was pronounced dead at the scene.
No other injuries have been reported.
The identity of the Mercedes driver has not been released.