David Cameron has warned that a vote to leave the European Union could increase the chances of Scottish independence.

The Prime Minister said that the issue was a “concern” and a reason to vote to stay in the EU in the poll on June 23.

His comments came just a week after Downing Street signalled for the first time that a vote to leave the EU could raise the prospect of a second independence referendum.

Campaigning in Suffolk, Mr Cameron said: “It is quite clear there are politicians in Scotland saying that a referendum to leave the EU could put that under question again.

“So I would say if, like me, you care about keeping our United Kingdom together, that is yet another reason to vote for staying in a reformed EU, rather than having uncertainty and instability in the relationships inside the United Kingdom.”

Yesterday, Nicola Sturgeon ruled out sharing a platform with Mr Cameron as she accused him of running a “miserable, negative and fear-based” EU campaign.

The First Minister also said she did not want Scotland to become independent as a result of a Brexit.

It would be bad for an independent Scotland to have its nearest neighbour outside the EU, she said.

Taking questions after a speech to the Resolution Foundation think tank in London, she said: “If Scotland were to vote in favour of EU membership and the rest of the UK were to vote to leave – if Scotland in other words was to be outvoted – then there is a real chance that that could lead to a second referendum on Scottish independence.”

But, she added: “It’s not what I want to happen. Of course, I do want Scotland to be independent, but I don’t want Scotland to become independent because the UK chooses to leave the EU.

“I want the UK as a whole to stay in the EU because I think that option will be better for the rest of the UK, I think it will be better for the EU and, should Scotland become independent in the future – something I believe will happen – I think it will be better for us too.”

Mr Cameron also rejected claims he was running a “Project Fear” campaign, after Conservative ministers warned it could take a decade to work out trade deals with the EU if the UK left.

Ministers also faced derision following claims holidaymakers could be stranded abroad amid a chaotic Brexit.

The Tory leader insisted that he was running a “Project Fact”.

But that claim was dismissed as “baloney” by his most high-profile Conservative opponent, Boris Johnson.

Ms Sturgeon also backed pro-Brexit ministers in an explosive row with the Prime Minister.

A number have protested after they were barred from seeing departmental papers on the referendum, amid allegations of a cover-up.

Rising star Priti Patel claimed the ban was “unconstitutional”.

Former Tory whip Michael Fabricant described the move as a “huge blunder”.

Ministers insisted it was the duty of civil servants to support the government of the day, while Mr Cameron tried to play down the dispute, saying it had been blown “out of proportion”.

Meanwhile, Swiss bank UBS predicted sterling would be hit hard if the UK left the EU.

The banking giant also estimated there was a 40 per cent chance that the UK will back a Brexit.

The Cabinet office review, titled Process for withdrawing from the European Union, described the two-year exit outlined in the EU treaties as unlikely.

In the absence of such an agreement UK citizens living, working or on holiday abroad could face immediate restrictions on their ability to “move about freely in Europe”.

The paper also warned that Britain could suffer 10 years of chaos with industries such as car manufacturing, farming and financial services hit.

Cabinet Office minister Matthew Hancock described the report as a “cautious assessment” of the implications of leaving the EU.

The document said a vote to leave the EU could lead to up to a decade or more of uncertainty.”

A spokesman for Ms Sturgeon said: “As the First Minister has made clear, a UK-wide vote to leave Europe while Scotland had voted to remain would almost certainly spark strong demands for a second independence referendum – especially given the No camp made Scotland’s’ place in the EU such a strong part of their campaign in 2014.”