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May, Nowell and Vunipola left out of squad
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England are 5.69/2 on the Betfair Exchange to win the Six Nations after new head coach Steve Borthwick announced his squad for the tournament that begins on 4 February.
Favourites Ireland 2.526/4 and defending Grand Slam champions France 2.915/8 are both shorter prices than England as the Red Rose begin a new era under Borthwick.
He succeeded Eddie Jones who was sacked after a run of five wins in 12 Tests.
The Betfair Sportsbook has a wide range of Six Nations markets where you can pick the winner, bet on a Triple Crown triumph and even bet on any Six Nations team to win the tournament and this autumn's Rugby World Cup.
France, who host the World Cup, are the shortest price of any nation to pull of that double at 13/2.
England's young team odds-on to beat Scotland
Billy Vunipola was left out of Borthwick's 36-man squad for the Six Nations and so were experienced wingers Jonny May and Jack Nowell.
Owen Farrell, who was confirmed as captain, will be available for England's opener against Scotland, despite the controversy over the terms of his suspension for making contact with Gloucester forward Jack Clement's head.
England are odds-on with Betfair Exchange punters to start with a win on 4 February.
They must take nothing for granted, though, after Scotland's famous 11-6 victory at Twickenham in 2021. Last year, Scotland won 20-17 against England at Murrayfield.
The same weekend, Wales host Ireland and reigning champions France begin their defence in Italy.
Borthwick gave first-time call-ups to Northampton fly-half Fin Smith, London Irish wing Ollie Hassell-Collins, Gloucester hooker George McGuigan, and Harlequins pair Cadan Murley and Jack Walker.
Dan Cole returns to the squad for the first time since the 2019 World Cup final.
Borthwick has selected a blend of youth and experience as England try to move on from a miserable autumn, improve on last year's third-placed finish in the Six Nations and build towards this autumn's World Cup.