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The index closed 4.36 points lower after gaining 4.26 points in the previous session.
Trading on the Ho Chi Minh Stock Exchange decreased by 19% to VND17.747 trillion (US$719.6 million).
The VN-30 basket, comprising the 30 largest capped stocks, saw 19 tickers fell.
HPG of steelmaker Hoa Phat Group saw a 1.7% decrease, HDB of HDBank went down 1.61% and SAB of brewer Sabeco closed 1.56% lower.
Ten blue chips gained. TPB of lender TPBank grew 2.3% while TCB of private lender Techcombank and PLX of fuel distributor Petrolimex both went up 1.0%.
Foreign investors were net buyers to the tune of VND254 billion, mainly buying TCB and FPT of IT giant FPT Corporation.
The HNX-Index for stocks on the Hanoi Stock Exchange, home to mid and small caps, fell 0.42%, while the UPCoM-Index for the Unlisted Public Companies Market was unchanged.
Globally, most stocks held firm on Wednesday, while oil prices and some safe haven assets rose, suggesting that the market impact of escalating Middle East tensions has been contained for now, Reuters reported.
Europe's benchmark STOXX index rose 0.24% and MSCI's broadest index of Asia-Pacific shares climbed 1.23%, despite fears of a wider conflict following Iran's ballistic missile strike on Israel.
Mainland Chinese markets were shut for the Golden Week holiday.
