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#!/usr/bin/perl

...
$str =~ s/[+-]?\d\w{4}//g;
$str =~ s/[+-]?\d\w+//g;
print $str;

#!/usr/bin/perl

...
my $str = ".,a..A,,C..+4ACGTG.,-2TG,,...,a";
$str =~ s/[+|-](\d*)(\w*)/(substr $2, $1)/ge;
print $str;