Kansas City (4-1), which closed as a 10½-point favorite, suffered its first loss of the season in a 19-13 defeat to Indianapolis on Sunday night at Arrowhead Stadium.
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South Point took a $55,000 bet on San Francisco minus 3½, the Westgate took a $33,000 wager on the Niners minus 4 and CG Technology took sharp bets on them at 3½ and 4.
Micah Roberts won the 2018 contest with a 52-32-1 record against the spread and will defend his title against a field that includes iconic broadcaster Brent Musburger.
Doug Fitz of Systemplays.com breaks down Week 1 of the NFL season.
The Patriots ascended from the 6-1 second choice, behind the Chiefs, to the 4-1 favorites at the Westgate sportsbook.
Cincinnati is a 20-1 long shot to win the AFC North, where the Browns and Steelers are plus 140 co-favorites and the Ravens are the 7-2 third choice.
Quarterbacks and coaches are the biggest keys to handicapping NFL preseason games.