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Bedfordshire North East MP Alistair Burt has announced he is stepping down from his frontbench role as Health Minister.
Mr Burt told MPs his decision had nothing to do with Brexit.
He informed David Cameron and Jeremy Hunt "a few weeks ago" that he would not be seeking a position in a reshuffled government.
He said he intends to continue his duties until September.
Raising a point of order at the end of health questions in the House of Commons, Mr Burt said: "Twenty-four years and one month ago I answered my first question as a junior minister in the House in oral questions and I have just completed my last oral questions.
This is not a sudden post-Brexit resignation - it's not catching.
A few weeks ago I made clear to the Secretary of State and to the Prime Minister and the Chief Whip that I wouldn't after the referendum be seeking a post in what I expected to be a reshuffled government and in the event I hope to carry on with my duties until September, but there won't be another oral questions."
Mr Burt said he wanted to take the opportunity to inform the House about his decision because most ministers "never know when the end will come".
He thanked MPs on both sides of the chamber for their "forbearance" as he said he is "looking forward to taking part in more questions from another seat in the chamber".
Commons Speaker John Bercow paid tribute to Mr Burt for being an "extremely popular and respected minister who commands widespread affection and loyalty in all parts of the House".
Labour's Valerie Vaz (Walsall South) echoed a similar sentiment.
Raising another point of order, she said: "Could I on behalf of everyone on this side pay tribute to Mr Burt. He has been an absolutely fantastic minister and he is a brilliant MP and long may he continue."
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