If the GPU is using legacy interrupts for some reason, it may be suffering from high latency while the CPU is busy handling other interrupt handlers for that IRQ.
Your motherboard's user manual specifies that the PCIE x16_1 slot (the top one) shares IRQ assignments with the internal graphics, HD Audio, USB 2.0 (EHCI), and PCI 2 slot.
Modern motherboards with PCIe are supposed to be exposing interrupts over a newer system, so the existence of this chart in your user manual is unexpected.
The PCIE x16_2 has its own IRQ assignment, so it does not have to compete with any other components to raise an interrupt request. If the GPU performs better in that slot, this may be the explanation for better performance.
However, that slot is only PCIe 8x.
With PCIe 8x you might lose performance in some programs that are bandwidth heavy. That won't have a significant impact on FPS for most games though.